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Atherosclerosis is a chronic condition characterized by impaired lipid homeostasis and chronic inflammatory pathology in large and mid-sized arteries. Myocardial infarction is caused by coronary artery thrombosis in a ruptured or unstable atherosclerotic plaque. Despite the emphasis on known triggering factors, such as hypertension and dyslipidemia, adverse events following MI, such as recurrence and mortality, are still high. Therefore, it is imperative to assess potential determinants of plaque instability. We evaluated markers of inflammation, extracellular matrix (ECM) remodeling, thrombosis, and lipids in first-time and recurrent MI (RMI). Two hundred patients diagnosed with MI within the first 24 h of the event were included in the study and categorized as first-time or recurrent MI. Serum levels of NF-κB, hs-CRP, TNF-α, IFN γ, IL-6, VCAM-1,MMP-9, stromelysin, TIMP-1, MCP-1, PAPP-A, vWF, D-dimer, PLA2, PON-1, Apo-B, Apo-A1, ox-LDL, and anti-oxidized LDL antibodies were analyzed by ELISA. We performed a multivariate logistic regression analysis for risk stratification. The mean age of first-time MI patients was 52.4 ± 25 years and that of recurrent MI patients was 55.9 ± 24.6 years. RMI patients showed significant ( Non-lipid factors provide substantial insights into plaque instability. Multiple markers of inflammation, thrombosis, extracellular matrix remodeling, and paroxonase-1 are reliable indicators of recurrent myocardial infarction. Show less

Dyslipidemia plays a very important role in the occurrence and development of cardiovascular disease (CVD). Genetic factors, including single nucleotide polymorphisms (SNPs), are one of the main risks of dyslipidemia. 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is not only the rate-limiting enzyme step of endogenous cholesterol production, but also the therapeutic target of statins. We investigated 405 Han Chinese and 373 Uyghur people who took statins for a period of time, recorded their blood lipid levels and baseline data before and after oral statin administration, and extracted DNA from each subject for SNP typing of In this study, for rs17671591, the CC We found that Show less

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) in the blood from an incredibly early age. This condition leads to the early development of atherosclerotic arterial diseases, which can manifest even in the first few decades of life. Mutations in genes related to the LDL receptor (LDL-R), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) are the main molecular mechanisms causing familial hypercholesterolemia. This case involves a 44-year-old Vietnamese female who presented at the emergency department with chest pain and was diagnosed with acute myocardial infarction (AMI) complicated by cardiogenic shock. Clinical signs and an elevated LDL-C level pointed to prolonged exposure to high cholesterol. A Dutch Lipid Clinic Network (DLCN) score of 10 further supported the diagnosis of FH. The reverse T-stenting and small protrusion (TAP) technique was selected and successfully employed to stent the LMCA, left anterior descending artery (LAD) and left circumflex artery (LCx). This technique was chosen due to its simplicity and rapid execution, making it particularly suitable in situations of cardiogenic shock where time-consuming procedures should be avoided. Genetic testing confirmed a heterozygous pathogenic mutation in the LDL-R gene, corroborating the clinical diagnosis of FH. The patient's condition has gradually stabilized, and they have been discharged from the hospital. The patient is currently being monitored as an outpatient at the cardiology clinic. This case emphasizes the importance of considering FH in patients with premature cardiovascular events by applying the clinical diagnostic criteria and confirming by genetic analysis. It also highlights advanced interventional techniques for managing complex coronary lesions, such as reverse TAP. Show less

Glaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP). The study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG. After adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 - -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 - -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 - -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 - -0.0008) in patients with POAG. Significantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk. Show less

Several studies indicated the ameliorating effects of raloxifene supplementation on apolipoproteins and blood pressure, although others have conflicting findings. Therefore, the present study was conducted in order to accurately and definitively understands the effect of raloxifene on apolipoprotein AI (Apo-AI), apolipoprotein B (APoB), lipoprotein (a) (Lp (a)), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in postmenopausal women. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Embase, and Web of Science and the Cochrane Library, through May 2024. The quality of studies was assessed using Cochrane tool. Random-effects meta-analysis was used to pool standardized mean differences (SMD) and 95 % CI for the outcomes. Twenty trials, with interventions ranging from 6 to 144 weeks and 2825 participants, were included. Raloxifene supplementation demonstrated significant reductions in ApoB (SMD: -0.92; 95 % CI: -1.49 to -0.35; P = 0.001), and Lp (a) (SMD: -0.25; 95 % CI: -0.39 to -0.11; P < 0.001) while increasing Apo-AI levels (SMD: 0.29; 95 % CI: 0.22-0.36; P < 0.001). Conversely, no significant effects were observed on SBP (WMD: -0.49 mmHg; 95 % CI: -3.01-2.04; P = 0.706), and DBP (WMD: -0.81 mmHg; 95 % CI: -4.04-2.41; P = 0.621). Moreover, subgroup analysis indicated that raloxifene significantly decreased DBP in studies with intervention durations of >12 weeks. This meta-analysis has shown that raloxifene supplementation may have beneficial effects on apolipoproteins in postmenopausal women. Future studies are needed to investigate the effect of raloxifene on health status in in postmenopausal women. Show less

Tamoxifen has been used in the management of breast cancer. The available evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins is controversial. Hence, this meta-analysis of randomized controlled trials (RCTs) was conducted to increase the quality of evidence on the effect of tamoxifen on lipoprotein(a) and apolipoproteins. Eligible RCTs published up to September 2023 were carefully selected following a comprehensive search. Thereafter, a meta-analysis was conducted using a random-effects model and the results were presented as the weighted mean difference (WMD) with a 95 % confidence interval (CI). The results from the random-effects model indicated a rise in ApoA-I (WMD: 16.24 mg/dL, 95 % CI: 5.35, 27.12, P = 0.003), and a decrease in ApoB (WMD: -9.37 mg/dL, 95 % CI: -15.16, -3.59, P = 0.001) and lipoprotein(a) (WMD: -3.24 mg/dL, 95 % CI: -5.66, -0.83, P < 0.001) concentrations following tamoxifen administration in women. Furthermore, a more pronounced decrease in ApoB (WMD: -12.86 mg/dL, 95 % CI: -19.78, -5.93, P < 0.001) and elevation in ApoA-1 levels (WMD: 51.97 mg/dL, 95 % CI: 45.89, 58.05, P < 0.001) were identified in a single study on patients with breast cancer. The current meta-analysis demonstrated an increase of ApoA-I and a decrease of ApoB and lipoprotein(a) levels after treatment with tamoxifen in women. Show less

APOBEC-1 complementation factor (A1CF) and Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-1 (APOBEC-1) constitute the minimal proteins necessary for the editing of apolipoprotein B (apoB) mRNA in vitro. Unlike APOBEC-1 and apoB mRNA, the ubiquitous expression of A1CF in human tissues suggests its unique biological significance, with various factors such as protein kinase C, thyroid hormones, and insulin regulating the activity and expression of A1CF. Nevertheless, few studies have provided an overview of this topic. We conducted a literature review to describe the molecular mechanisms of A1CF and its relevance to human diseases. In the PubMed database, we used the keywords 'A1CF' and 'APOBEC-1 complementation factor' to collect peer-reviewed articles published in English from 2000 to 2023. Two authors independently reviewed the articles and reached the consensus. After reviewing 127 articles, a total of 61 articles that met the inclusion criteria were included in the present review. Studies revealed that A1CF is involved in epigenetic regulation of reproductive cells affecting embryonic development, and that it is closely associated with the occurrence of gout due to its editing properties on apoB. A1CF can also affect the process of epithelial-mesenchymal transition in renal tubular epithelial cells and promote liver regeneration by controlling the stability of IL-6 mRNA, but no influence on cardiac function was found. Furthermore, increasing evidence suggests that A1CF may promote the occurrence and development of breast cancer, lung cancer, renal cell carcinoma, hepatocellular carcinoma, endometrial cancer, and glioma. This review clarifies the association between A1CF and other complementary factors and their impact on the development of human diseases, aiming to provide guidance for further research on A1CF, which can help treat human diseases and promote health. Show less

Retention of apolipoprotein B (apoB)-containing lipoproteins within the arterial wall plays a major causal role in atherosclerotic cardiovascular disease (ASCVD). There is a single apoB molecule in all apoB-containing lipoproteins. Therefore, quantitation of apoB directly estimates the number of atherogenic particles in plasma. ApoB is the preferred measurement to refine the estimate of ASCVD risk. Low-density lipoprotein (LDL) particles are by far the most abundant apoB-containing particles. In patients with elevated lipoprotein(a) (Lp(a)), apoB may considerably underestimate risk because Mendelian randomization studies have shown that the atherogenicity of Lp(a) is approximately 7-fold greater than that of LDL on a per apoB particle basis. In subjects with increased Lp(a), the association between LDL-cholesterol and incident CHD (coronary heart disease) is increased, but the association between apoB and incident CHD is diminished or even lost. Thus, there is a need to understand the mechanisms of Lp(a), LDL-cholesterol and apoB-related CHD risk and to provide clinicians with a simple practical tool to address these complex and variable relationships. How can we understand a patient's overall lipid-driven atherogenic risk? What proportion of this risk does apoB capture? What proportion of this risk do Lp(a) particles carry? To answer these questions, we created a novel metric of atherogenic risk: risk-weighted apolipoprotein B. In nmol/L: Risk-weighted apoB = apoB - Lp(a) + Lp(a) x 7 = apoB + Lp(a) x 6. Proportion of risk captured by apoB = apoB divided by risk-weighted apoB. Proportion of risk carried by Lp(a) = Lp(a) × 7 divided by risk-weighted apoB. Risk-weighted apoB agrees with risk estimation from large epidemiological studies and from several Mendelian randomization studies. ApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB. Show less

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce the protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3'-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver-derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion. Show less

Familial hypercholesterolemia (FH) is a genetic disorder that results in elevated low-density lipoprotein cholesterol (LDL-C) levels, which manifest early in the first decades of life. It is a major cause of premature coronary artery disease worldwide, leading to significant public health challenges. The prevalence of genetically determined FH in patients with premature coronary artery disease remains underestimated, particularly in developing countries. This study aimed to assess the prevalence of genetically defined FH in Vietnamese patients with premature acute myocardial infarction (AMI) in the Vietnamese population. This cross-sectional study enrolled 218 consecutive patients diagnosed with premature AMI who underwent coronary angiography. The low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 genes were analyzed by next-generation sequencing. FH was diagnosed according to Dutch Lipid Clinic Network criteria. Among the patients with premature AMI who underwent coronary angiography, the mean age was 46.9 ± 6.1 years, with a predominance of males (83.9%). The prevalence of potential FH diagnosed using Dutch Lipid Clinic Network criteria was 14.7% (definite FH, 6.0%; probable FH, 8.7%). Pathogenic or likely pathogenic variants in LDLR, apolipoprotein B, and proprotein convertase subtilisin-kexin type 9 were found in 9 of 218 patients (4.1%), all of which were causative mutations in LDLR. Patients with premature AMI and FH had significantly greater LDL-C levels (217.6 vs 125.7 mg/dL) and more severe coronary artery lesions, as assessed by the Gensini score (100.3 vs 60.5), than did those in the No FH group. The prevalence of genetically determined FH among Vietnamese patients with premature AMI is relatively high. Screening and diagnosis of hereditary conditions in patients with premature AMI are essential to improve early detection and management and reduce the burden of coronary artery disease in this population. Show less

Recently, a new hereditary disease, bovine lymphocyte intestinal retention defect (BLIRD), was discovered in Holstein cattle in France and is caused by a variant in the Integrin subunit beta 7 (ITGB7) gene. The altered cell adhesion molecule resulting from this point mutation is responsible for an impaired tissue of CD4 T lymphocytes from the blood to intestinal tissue. The aim of this study was to assess the allelic frequency of this deleterious variant in the local Holstein population and to clinically examine ten BLIRD-affected Holstein cattle from Switzerland in order to characterise the phenotype of this new hereditary disease, which is still unknown to the veterinary community. BLIRD was associated with severely impaired animal health in the rearing phase and significantly reduced animal welfare due to weakened immune defences, below-average development and recurrent diarrhoea. Further examinations revealed increased leucocyte values and a slightly increased average age at first calving. Affected homozygous animals are labelled internationally as BLIRD-carrier homozygous (LRS), BLIRD-carrier heterozygous (LRC) and BLIRD-free (LRF). An obvious inbreeding practice was clearly demonstrated by the pedigree analysis of the ten animals, which all trace back to the potential founder bull. Herein, BLIRD has been detected and described in Switzerland for the first time. The ITGB7 variant allele has a frequency of 2,1 % in the current Swiss Holstein population, which is below the level of the cholesterol deficiency (CD)-associated apolipoprotein B (APOB) variant allele with a frequency of 3,9 %. Although relatively rare, attention should be paid to the BLIRD genotype when mating in order to exclude further affected animals. In cattle with clinically suspected BLIRD, the diagnosis should be confirmed by genetic testing. Show less

To review the development of oral agents to lower Lp(a) levels as an approach to reducing cardiovascular risk, with a focus on recent advances in the field. Extensive evidence implicates Lp(a) in the causal pathway of atherosclerotic cardiovascular disease and calcific aortic stenosis. There are currently no therapies approved for lowering of Lp(a). The majority of recent therapeutic advances have focused on development of injectable agents that target RNA and inhibit synthesis of apo(a). Muvalaplin is the first, orally administered, small molecule inhibitor of Lp(a), which acts by disrupting binding of apo(a) and apoB, in clinical development. Nonhuman primate and early human studies have demonstrated the ability of muvalaplin to produce dose-dependent lowering of Lp(a). Ongoing clinical trials will evaluate the impact of muvalaplin in high cardiovascular risk and will ultimately need to determine whether this strategy lowers the rate of cardiovascular events. Muvalaplin is the first oral agent, developed to lower Lp(a) levels. The ability of muvalaplin to reduce cardiovascular risk remains to be investigated, in order to determine whether it will be a useful agent for the prevention of cardiovascular disease. Show less

This investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). This prospective, open-label, randomized study included non-diabetic participants with metabolic syndrome and intrahepatocellular lipid (IHCL) levels >10 %, as determined by proton magnetic resonance spectroscopy ( Thirty-two participants completed the study. Rosuvastatin resulted in a significant absolute (△IHCL: 7.61 ± 4.51 vs. 1.54 ± 5.33, p = 0.002) and relative reduction in IHCL (△IHCL%: -42.28 ± 24.90 % vs. -8.91 ± 31.93 %, p = 0.003) compared to the control. Reduction in IHCL correlated significantly with decreases in low-density lipoprotein cholesterol (LDL-C) (r = 0.574, p < 0.01), apolipoprotein B (ApoB) (r = 0.660, p < 0.001), and free fatty acids (FFA) (r = 0.563, p = 0.005). No significant safety differences were observed between groups. Rosuvastatin significantly reduced hepatic steatosis in individuals with moderate to severe MAFLD and metabolic syndrome over 52 weeks, while maintaining a favorable safety profile. Show less

Triglyceride-rich lipoproteins and remnants (TRL/remnants) have a causal, but not yet quantified, relationship with coronary heart disease (CHD): myocardial infarction plus revascularization. The authors sought to estimate TRL/remnant per-particle atherogenicity, investigate causal relationships with inflammation, and determine whether differences in the atherogenicity of TRL/remnants and low-density lipoprotein (LDL) impact the causal association of non-high-density lipoprotein cholesterol (non-HDL-C) with CHD. Single nucleotide polymorphisms (SNPs) (N = 1,357) identified by genome-wide association in the UK Biobank were ranked into 10 clusters according to the effect on TRL/remnant-C vs LDL-C. Mendelian randomization analysis was used to estimate for each SNP cluster CHD ORs per 10 mg/dL apolipoprotein B (apoB) and per 0.33 mmol/L non-HDL-cholesterol, and to evaluate association of TRL/remnants with biomarkers of systemic inflammation. SNPs in cluster 1 predominantly affected LDL-C, whereas SNPs in cluster 10 predominantly affected TRL/remnant-C. CHD risk per genetically predicted increase in apoB and in non-HDL-C rose across clusters. ORs per 10 mg/dL higher apoB was 1.15 (95% CI: 1.11-1.19) in cluster 1 vs 1.70 (95% CI: 1.52-1.90) in cluster 10. Comparing ORs between these TRL/remnant-predominant and LDL-predominant clusters, we estimated that TRL/remnants were at least 3.9 (95% CI: 2.8-5.4) times more atherogenic than LDL on a per-particle basis. For non-HDL-C, CHD ORs per 0.33 mmol/L rose from 1.15 (95% CI: 1.11-1.19) for cluster 1 to 1.40 (95% CI: 1.30-1.50) for cluster 10. TRL/remnants exhibited causal relationships with inflammation, but this did not explain their greater atherogenicity. TRL/remnants are about 4 times more atherogenic than LDL. Variation in the causal association of non-HDL-C with CHD indicates that adjustment for percentage TRL/remnant-C may be needed for accurate risk prediction. Show less

Lipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA. We tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA. Elevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02). Both observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists. Show less

In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors. Show less

Case-control, intervention and laboratory studies have demonstrated a link between apolipoprotein B (ApoB)-containing lipoproteins and clot structure and thrombosis. There is, however, limited evidence on a population level. We determined the cross-sectional relationship between lipoprotein(a) [Lp(a)], low-density lipoprotein cholesterol (LDL-C), and ApoB with fibrinogen and plasma clot properties in 1462 Black South Africans, a population with higher fibrinogen and Lp(a) levels compared with individuals of European descent. Data were obtained from participants in the South African arm of the Prospective Urban and Rural Epidemiology study. Clot properties analyzed included lag time, slope, maximum absorbance, and clot lysis time (turbidity). Lp(a) was measured in nM using particle-enhanced immunoturbidimetry. General linear models (GLM) were used to determine the associations between ApoB and ApoB-containing lipoproteins with fibrinogen and plasma clot properties. Stepwise regression was used to determine contributors to clot properties and Lp(a) variance. GLM and regression results combined, indicated fibrinogen concentration and rate of clot formation (slope) had the strongest association with Lp(a); clot density associated positively with both Lp(a) and LDL-C; time to clot formation associated negatively with ApoB; and clot lysis time (CLT) demonstrated strong positive associations with both ApoB and LDL-C, while its association with Lp(a) was fibrinogen concentration dependent. These findings suggest that ApoB and the lipoproteins carrying it contribute to prothrombotic clot properties in Africans on an epidemiological level and highlight potential novel prothrombotic roles for these (apo)lipoproteins to be considered for the development of targeted therapeutic approaches to address thrombotic conditions related to clot properties. Show less

It remains unclear whether lipid profiles and lipid-lowering medications are causally related to peripheral arterial disease (PAD). Explain whether there is a causal relationship between lipid status and lipid-lowering drugs and PAD. In this two-sample Mendelian randomization (MR) analysis, we assessed the causal relationship between lipid traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), total cholesterol (TC), and LDL-associated genetic variants (HMGCR, NPC1L1, PCSK9, APOB), and the risk of PAD using genetic variants associated with these lipid markers. The study analyzed data from 1,654,960 individuals derived from the Global Lipid Genetics Consortium and the UK Biobank, ensuring a robust and comprehensive genetic insight into the effects of lipid dysfunction on PAD. We found genetically predicted associations between HDL-C (OR: 0.83, 95% CI: 0.83-0.77), LDL-C (OR: 1.29, 95% CI: 1.12-1.50), TC (OR: 1.14, 95% CI: 1.01- 1.29), TG (OR: 1.16, 95% CI: 1.04-1.24), APOB (OR: 1.31, 95% CI: 1.16-1.48), and APOA1 (OR: 0.84, 95% CI: 0.77-0.97), and the risk of PAD. In addition, inhibition of PCSK9 was associated with a reduced risk of PAD (OR: 0.68, 95% CI: 0.57-0.79, P<0.001), while no association between the other three gene proxies of LDL inhibition including HMGCR (OR: 1.21, 95% CI: 0.87-1.69, P=0.250), NPC1L1 (OR: 0.77, 95% CI: 0.44-1.33, P=0.344), and APOB (OR: 1.01, 95% CI: 0.87-1.26, P=0.890), and the risk of PAD were found. Based on genetic evidence, dyslipidemia is an important risk factor for PAD. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may be an effective strategy for the treatment of PAD. Show less

Heat stress is the most common environmental stressor in poultry production, negatively affecting growth performance, meat quality, and welfare. Therefore, the aim of this study was to compare the nutritional effects of dietary supplementation with selenomethionine, Bacillus subtilis (BS), and a combination of selenomethionine and BS on broilers challenged with heat stress. A total of 300 21-day-old male broilers (Ross 308) were randomly assigned to 5 groups with 6 replicates of 10 broilers per each: control group (CON, broilers raised at 22 ± 2 °C), heat stress exposure group (HS, broilers raised at 32 ± 2 °C for 8 h/d), HSS group (HS group supplemented with 0.3 mg/kg selenomethionine), HSB group (HS group supplemented with 1 × 109 cfu/kg BS), and HSBS group (HS group supplemented with 0.3 mg/kg selenomethionine and × 109 cfu/kg BS). The experiment lasted for 21 d. The results indicated that, compared to the CON group, heat stress reduces (P < 0.05) broiler growth performance and damages the meat quality in breast and thigh muscles. Dietary supplementation with selenomethionine and BS did not improve the growth performance of broilers under heat stress. However, compared to the HS group, the HSS, HSB, and HSBS groups showed significantly increased (P < 0.05) pH45 min, redness (a*) and yellowness (b*), muscle fiber density, intramuscular fat, triglyceride content, and expression levels of Myf5, CAPN 2, FM, SLC27A1, A-FABP, H-FABP, APOB-100, and ACC in breast and thigh muscles. Meanwhile, these groups showed reduced (P < 0.05) lightness (L*), drip loss, shear force, muscle fiber cross-sectional area, and FM gene expression level. The HSBS group showed greater improvement in the physicochemical quality of muscle and volatile substances compared to the HSS and HSB groups. In conclusion, selenomethionine and BS improved meat quality and flavor in broilers under heat stress by modulating muscle fiber composition and characteristics, as well as increasing intramuscular fat deposition. Show less

Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease. To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints. Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People's Hospital of Chengdu (FPHC). The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient's cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed. Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth. ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints. Show less

We aimed to determine the genetic risk factors in patients aged 45 years and below with a history of early myocardial infarction (MI), compared to individuals over 60 years of age with no history of MI. In this study, we selected different age groups to more clearly distinguish genetic differences. Accordingly, we compared individuals who had experienced MI at an early age with those who were older and had not experienced any cardiovascular events. The patient group consisted of 99 volunteers under the age of 45 with a history of MI, while the control group included 99 volunteers aged 60 and over without a history of MI. MTHFR (C677T, A1298C), Factor V Leiden (G1691A), Prothrombin (G20210A), PAI (4G/5G), Factor XIII (V34L), APOA1 (rs670, rs1799837, rs5069), and APOB were studied using blood samples taken from the patients. In the logistic regression analysis of thrombophilia markers and gene polymorphisms in the patient and control groups, no statistically significant increase was observed in markers other than APOA1 rs5069 gene polymorphism. APOA1 rs5069 gene polymorphism was found to be higher in the patient group than those without this polymorphism. The frequencies of homozygous MTHFR (C677T, A1298C) and heterozygous Factor XIII V34L were higher in the patient cohort compared to the controls. In our study, we found that prothrombotic gene variants and APOA1 rs5069 polymorphism were statistically significantly associated with coronary artery disease. Thus, prothrombotic gene variants and APOA1 rs5069 polymorphism may serve as predictors of early myocardial infarctions. Individuals with early family histories of coronary artery disease could be screened for these mutations. Show less

Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms. This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1β, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI. There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI). LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque. ChiCTR2200058529; Date of registration: 2022-04-10. Show less

Dyslipidemia stands as an autonomous peril in the realm of atherosclerotic cardiovascular maladies. Prompt identification and timely intervention in the case of dyslipidemia hold promise for substantially curbing the onset and fatality rates associated with coronary heart disease. Traditional lipid surveillance metrics employed in clinical settings, such as low-density lipoprotein cholesterol, exhibit notable limitations. Conversely, lipid-derived parameters emerge as formidable contenders, demonstrating a capacity to amalgamate and quantify disparate risk factors and multifactorial etiologies inherent in a given disease. By encompassing a broader spectrum of information than singular indices, these parameters offer a more profound insight into disease progression by virtue of their grounding in the physiological intricacies of lipid metabolism. Drawing upon extant domestic and international guidelines and research, this discourse delineates and synthesizes four lipid-derived parameters with promising clinical applications: atherogenic index of plasma, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, apolipoprotein B/A1 ratio, and lipoprotein combine index, and forwards a perspective grounded in current strides in clinical research. Show less

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease associated with obesity and is caused by the accumulation of ectopic fat without alcohol consumption. Coxsackievirus and adenovirus receptor (CAR) are vital for cardiac myocyte-intercalated discs and endothelial cell-to-cell tight junctions. CAR has also been reported to be associated with obesity and high blood pressure. However, its function in the liver is still not well understood. The liver of obese mice exhibit elevated CAR mRNA and protein levels. Furthermore, in the liver of patients with non-alcoholic steatohepatitis, CAR is reduced in hepatocyte cell-cell junctions compared to normal levels. We generated liver-specific CAR knockout (KO) mice to investigate the role of CAR in the liver. Body and liver weights were not different between wild-type (WT) and KO mice fed a paired or high-fat diet (HFD). However, HFD induced significant liver damage and lipid accumulation in CAR KO mice compared with WT mice. Additionally, inflammatory cytokines transcription, hepatic permeability, and macrophage recruitment considerably increased in CAR KO mice. We identified a new interaction partner of CAR using a protein pull-down assay and mass spectrometry. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) demonstrated a complex relationship with CAR, and hepatic CAR expression tightly regulated its level. Moreover, Apolipoprotein B (ApoB) and Low-density lipoprotein receptor (LDLR) levels correlated with APOBEC3C expression in the liver of CAR KO mice, suggesting that CAR may regulate lipid accumulation by controlling APOBEC3C activity. In this study, we showed that hepatic CAR deficiency increased cell-to-cell permeability. In addition, CAR deletion significantly increased hepatic lipid accumulation by inducing ApoB and LDLR expression. Although the underlying mechanism is unclear, CARs may be a target for the development of novel therapies for MAFLD. Show less

Apolipoprotein B (ApoB) and lipoprotein (a) (Lp[a]) are predictors of cardiovascular disease (CVD) risk; therefore, current recommendations for CVD risk assessment and management advocate that patients receive testing for ApoB and Lp(a) in addition to the standard lipid panel. However, US guidelines around ApoB and Lp(a) testing have evolved over time and vary slightly by expert committee. The objective of this analysis was to estimate the number of insured individuals in the USA who received any component of a lipid test, or ApoB and/or Lp(a) testing, during 2019. We conducted a cross-sectional analysis to estimate the prevalence of any component of a lipid test, ApoB, and/or Lp(a) in the USA using four different claim data sources (including Medicaid, Medicare, and commercially insured enrollees). Prevalence estimates were age-, sex-, payor-, and region-standardized to the 2019 US Annual Social and Economic Supplement of the Current Population Survey. We also described the clinical profile of patients who received lipid testing between 2019 and 2021 (cohort analysis) in Optum claims database. Enrollees were grouped into four non-mutually exclusive cohorts based on their completion of any component of the lipid panel, ApoB, Lp(a), or ApoB and Lp(a). In the prevalence cohort, over a third (38 %) of insured adults in the USA underwent testing for any component of a lipid panel in 2019. This proportion was higher for individuals aged ≥65 years compared to younger adults (62% vs 31 %). The proportion of ApoB and Lp(a) testing represented only <1 % of testing for any component of a lipid panel. In the cohort analysis, we found that lipid testing increased with age and comorbidities. These data should be considered by guideline-issuing agencies and organizations to develop education campaigns encouraging more frequent use of tests beyond the standard lipid panel. Show less

The polar bear (Ursus maritimus) occupies a relatively narrow ecological niche, with many traits adapted for cold temperatures, movement across snow, ice and open water, and for consuming highly lipid-dense prey species. The divergence of polar bears from brown bears (Ursus arctos) and their adaptation to their Arctic lifestyle is a well-known example of rapid evolution. Previous research investigating whole genomes uncovered twelve key genes that are highly differentiated between polar and brown bears, show signatures of selection in the polar bear lineage, and are associated with polar bear adaptation to the Arctic environment. Further research suggested fixed derived alleles in these genes arose from selection on both standing variation and de novo mutations in the evolution of polar bears. Here, we reevaluate these findings based on a larger and geographically more representative dataset of 119 polar bears and 135 brown bears, and assess the timing of derived allele fixation in polar bears by incorporating the genomes of two Late Pleistocene individuals (aged 130-100,000 years old and 100-70,000 years old). In contrast with previous results, we found no evidence of derived alleles fixed in present-day polar bears within the key genes arising from de novo mutation. Most derived alleles fixed in present-day polar bears were also fixed in the Late Pleistocene polar bears, suggesting selection occurred prior to 70,000 years ago. However, some derived alleles fixed in present-day polar bears were not fixed in the two Late Pleistocene polar bears, including at sites within APOB, LYST, and TTN. These three genes are associated with cardiovascular function, metabolism, and pigmentation, suggesting selection may have acted on different loci at different times. Show less

To investigate the role of body mass index (BMI), serum lipid profile molecules and their derivative indexes in colorectal polyps. A total of 352 individuals who underwent colonoscopy at our center were included in this retrospective analysis. Of these, 247 patients without evident abnormalities (control group), while 105 patients diagnosed with colorectal polyps (patient group). Serum lipid profile molecules and their derivative indexes were then compared between the two groups. The patient group exhibited significantly higher levels of total cholesterol (TC) and apolipoprotein B (ApoB) compared to the control group (p<0.05). In males, the patient group displayed elevated levels of ApoB and ApoB/ApoA1 ratio compared to the control group (p<0.05). Additionally, the triglycerides (TG) and TG/high-density lipoprotein-cholesterol (HDL-C) ratios were significantly higher in the multiple polyps group than in the single polyp group (p<0.05). Furthermore, the HDL-C and HDL-C/ApoA1 ratio levels were higher in the adenomatous polyp group when compared to the non-adenomatous polyp group (p<0.05). Multiple logistic regression analysis indicated that total cholesterol (TC), TG, low-density lipoprotein-cholesterol (LDL-C), TC/HDL-C ratio, TG/HDL-C ratio and LDL-C/HDL-C ratio were risk factors for the occurrence of colorectal polyps (p<0.05). ROC curve analyses revealed that TC, ApoB, and ApoB/ApoA1 ratio were associated with colorectal polyps. No significant difference in BMI between the two groups (p>0.05). The incidence and progression of colorectal polyps are linked to serum lipid molecules and their derivative indexes. Dyslipidemia may increase the risk of colorectal polyps, potentially leading to colorectal cancer (CRC). Show less

Blood lipid levels were associated with chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), but the genetic basis and causal nature remain unclear. This study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D. Our prospective analysis involved 8,607 White participants with T2D but no CKD at baseline from the UK Biobank. Five common lipid traits were included as exposures. Weighted genetic risk scores (GRSs) for these lipid traits were developed. The causal associations between lipid traits, as well as lipid fractions, and CKD were explored using linear or nonlinear Mendelian randomization (MR). The 10-year predicted probabilities of CKD were evaluated via integrating MR and Cox models. Higher GRS of apolipoprotein B (ApoB) was associated with an increased CKD risk (hazard ratio (HR) [95% confidence interval (CI)]:1.07[1.02,1.13] per SD; P = 0.008) after adjusting for potential confounders. Linear MR indicated a positive association between genetically predicted ApoB levels and CKD (HR [95% CI]:1.53 [1.12,2.09]; P = 0.008), but no evidence of associations was found between other lipid traits and CKD in T2D. Regarding 12 ApoB- containing lipid fractions, a significant causal association was found between medium very-low-density lipoprotein particles and CKD (HR[95% CI]:1.16[1.02,1.32];P = 0.020). Nonlinear MR did not support nonlinearity in these causal associations. The 10-year probability curve showed that ApoB level was positively associated with the risk of CKD in patients with T2D. Lower ApoB levels were causally associated with a reduced risk of CKD in patients with T2D, positioning ApoB as a potential therapeutic target for CKD prevention in this population. Show less