👤 Sara Borghi

Direct measurement of apolipoprotein B (ApoB) is not always standardized and is relatively expensive, making it unavailable in several low-income settings. To address this issue, several formulas have been developed to estimate ApoB levels. Therefore, our study aims to compare the reliability of 23 formulas for estimating ApoB levels in a large cohort of South-European individuals. We retrospectively assessed 4.577 clinical records in which ApoB measurements were obtained using the same standardized method. Overall concordance was defined as the proportion of cases where the directly measured ApoB level fell within the same category as the estimated ApoB level, based on ApoB quartiles (<80 mg/dL, 80-94 mg/dL, 95-114 mg/dL, and ≥115 mg/dL). In addition, overall concordance was assessed for different lipoprotein(a) (Lp(a)) and non-high density lipoprotein cholesterol (non-HDL-C) sub-levels. Ordinary least squares linear regression analyses were performed to compare estimated and measured ApoB values. Residual error plots were generated to visualize the difference between each estimation method and the actual ApoB measurements, stratified by Lp(a) and non-HDL-C levels. Plasma ApoB levels were best predicted by a non-HDL-C based formula and a formula using Friedewald's low-density lipoprotein cholesterol (LDL-C), regardless of ApoB plasma levels. Non-HDL-C levels did not significantly affect the concordance between measured and estimated ApoB across the different formulas, except at low non-HDL-C levels. Similarly, Lp(a) levels did not significantly impact concordance. However, the highest concordance level was 41 %. Some simple formulas based on low-cost and widely available parameters can estimate ApoB levels independently of ApoB, non-HDL-C, and Lp(a) plasma levels. This approach may be particularly useful for estimating ApoB levels in low-resource settings. Show less

During skeletal myogenesis, the zinc-finger transcription factors SNAI1 and SNAI2, are expressed in proliferating myoblasts and regulate the transition to terminally differentiated myotubes while repressing pro-differentiation genes. Here, we demonstrate that SNAI1 is upregulated in vivo during the early phase of muscle regeneration induced by bupivacaine injury. Using shRNA-mediated gene silencing in C2C12 myoblasts and whole-transcriptome microarray analysis, we identified a collection of genes belonging to the endoplasmic reticulum (ER) stress pathway whose expression, induced by myogenic differentiation, was upregulated in absence of SNAI1. Among these, key ER stress genes, such as Atf3, Ddit3/Chop, Hspa5/Bip, and Fgf21, a myokine involved in muscle differentiation, were strongly upregulated. Furthermore, by promoter mutant analysis and Chromatin immune precipitation assay, we demonstrated that SNAI1 represses Fgf21 and Atf3 in proliferating myoblasts by directly binding to multiple E boxes in their respective promoter regions. Together, these data describe a new regulatory mechanism of myogenic differentiation involving the direct repressive action of SNAI1 on ER stress and Fgf21 expression, ultimately contributing to maintaining the proliferative and undifferentiated state of myoblasts. Show less

The term phenocopy indicates a condition that imitates one produced by a gene and is also used for acquired Brugada-like ECG manifestations. Cases of Brugada phenocopies are increasingly reported in literature and an international registry is ongoing. We describe two patients with Hypertrophic Cardiomyopathy (HCM) and Brugada ECG pattern. Both patients carried the same pathogenic splicing mutation in MYBPC3 gene (responsible for HCM) while no genetic mutation associated with Brugada Syndrome was identified. To the best of our knowledge, Brugada ECG pattern has been rarely reported in patients with HCM. Show less

Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects. Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development. Our aim is to describe the main pharmacodynamic and pharmacokinetic characteristics, the available efficacy, tolerability and safety data obtained in randomized clinical trials where these drugs were tested. Expert opinion: Non-statin lipid-lowering drugs can be considered an excellent strategy to reduce the residual CV risk, also represented by non-target LDL-C values and high lipoprotein(a) serum levels. In particular, the approved PCSK9 inhibitors (Evolocumab and Alirocumab) have been very effective in optimizing plasma LDL-C values and reducing CV event risk. Show less