👤 Andreas Ritsch

Cardiovascular disease (CVD) is a systemic multifocal illness called atherosclerosis that causes artery constriction and blockage. By causing cholesterol to build up in the artery wall, hypercholesterolemia is a major factor in the pathophysiology of atherosclerotic plaque development. Reverse cholesterol transport is the process of transporting cholesterol from the periphery back to the liver through cholesterol efflux mediated by high-density lipoprotein (HDL). It was suggested that the cholesterol efflux capacity (CEC), which is inversely linked with cardiovascular risk, can serve as a stand-in measure for reverse cholesterol transport. In this work, we sought to investigate a potential link between the peripheral plaque volume (PV) and CEC. Since lipid-lowering therapy interferes with CEC, we performed a cross-sectional study of 176 patients (48.9% females) with one cardiovascular risk factor or known CVD that did not currently take lipid-lowering medication. CEC was determined using cAMP-treated In our patients, we discovered an inverse relationship between high total PV and CEC ( In patients not receiving lipid-lowering treatment, CEC inversely correlates with peripheral atherosclerosis, supporting its role in the pathophysiology of atherosclerosis. Show less

Green tea is associated with decreased risk for cardiovascular disease and stroke. Matcha is a special kind of powdered green tea known for its use in the Japanese tea ceremony. Due to its influence on lipoprotein parameters, it has been postulated to exert antiatherogenic effects. This study investigates whether it modulates the high-density lipoprotein (HDL) function and thereby influences the atherogenic process in an animal model with a strong influence on humans' situation. After a pretreatment phase based on a standard diet, 10 female New Zealand White (NZW) rabbits are fed a high-fat diet for 20 weeks. The treatment group is additionally administered 1% matcha during the whole experiment. Long-term matcha treatment leads to lowered HDL cholesterol, impaired cholesterol transport manifested by reduced in vitro cholesterol efflux capacity, reduced cholesteryl ester transfer protein (CETP)-mediated cholesterol ester (CE) transfer between HDL and triglyceride-rich particles, and reduced macrophage-specific in vivo transfer, where ian increased absorption of cholesterol in the liver but a decreased secretion into bile is observed. Pulse wave velocity, assessed by nuclear magnetic resonance, is increased in matcha-treated animals, and a similar trend is observed for atherosclerotic lesion formation. Long-term matcha green tea treatment of hypercholesterolemic rabbits cause impaired reverse cholesterol transport and increased vascular stiffness, and susceptibility for atherosclerotic lesion development. Show less

Very rare loss-of-function mutations in the apolipoprotein C3 (APOC3) gene have been associated with low circulating apoC-III, low triglycerides, and reduced cardiovascular risk. We aimed to analyze the impact of common APOC3 variants on key parameters of lipid metabolism and coronary artery disease in the largest sample so far. Common variants in APOC3 were tested for associations with circulating apoC-III, lipids, and apolipoprotein B (apoB) in 3041 participants of the LUdwigshafen RIsk and Cardiovascular health study (LURIC). These variants were then tested for associations with coronary artery disease in a meta-analysis comprising up to 332,389 participants of the CARDIOGRAMplusC4D consortium and the UK Biobank. The mean (standard deviation) apoC-III concentration was 14.6 (5.1) mg/dl. Seven common variants in APOC3 (rs734104, rs4520, rs5142, rs5141, rs5130, rs5128, and rs4225) were associated with circulating apoC-III (all p < 0.05). The alleles that modestly raised apoC-III were also associated with markedly higher total triglycerides and very low density lipoprotein (VLDL) triglycerides and cholesterol (all p < 0.05), but not with low density lipoprotein (LDL) cholesterol and total apoB (all p > 0.05). These variants were not associated with coronary artery disease in the CARDIOGRAMplusC4D consortium and the UK Biobank (all p > 0.1). Modest, genetically caused elevations of apoC-III are associated with a marked increase of triglyceride-rich lipoproteins but not with an increase of LDL cholesterol, total apoB, and coronary artery disease. Whether effective inhibition of apoC-III production with antisense oligomers will be instrumental to reduce cardiovascular risk remains to be demonstrated. Show less

Rabbits with naturally high levels of cholesterol ester transfer protein (CETP), unlike rodents, have become an interesting animal model for the study of lipid metabolism and atherosclerosis, as they have similarities to humans in lipid metabolism, cardiovascular physiology and susceptibility to develop atherosclerosis. Rodents, such as mice, are not prone to atherosclerosis as they lack the mass and activity of CETP, as a key player in lipoprotein metabolism. Recently, APOE-knockout in rabbits has been shown to promote atherosclerosis and associated premature IVD degeneration that mimic the symptoms of atherosclerosis and structural changes of IVDs in humans. Here we examined whether APOE-knockout promoted IVD degeneration in rabbits is associated with imbalanced inflammatory catabolic activities, as the underlying problem of biological deterioration that mimic the symptoms of advanced IVD degeneration in humans. We analysed in lumbar nucleus pulposus (NP) of APOE-knockout rabbits the cell viabilities and the intracellular levels of inflammatory, catabolic, anti-catabolic and anabolic proteins derogating IVD matrix. Grades of IVD degeneration were evaluated by magnetic resonance imaging. NP cells were isolated from homozygous APOE-knockout and wild-type New Zealand White rabbits of similar age. Three-dimensional cell culture with low-glucose was completed in alginate hydrogel. Cell proliferation and intracellular levels of target proteins were examined by MTT and ELISA assays. Alike human NP cells of different disc degeneration grades, NP cells of APOE-knockout and wild-type rabbits showed significantly different in vivo cell population densities (p<0.0001) and similar in vitro proliferation rates. Furthermore, they showed differences in overexpression of selective inflammatory and catabolic proteins (p<0.0001) similar to those found in human NP cells of different disc degeneration grades, such as IL-1β, TNF-α, ADAMTS-4, ADAMTS-5 and MMP-3. This study showed that premature IVD degeneration in APOE-knockout rabbits was promoted by the accumulation of selective inflammatory catabolic factors that enhanced imbalances between catabolic and anabolic factors mimicking the symptoms of advanced IVD degeneration in humans. Thus, APOE-knockout rabbits could be used as a promising model for therapeutic approaches of degenerative disc disorders. Show less

Obesity is associated with a lower HDL-mediated cholesterol efflux from macrophages and a higher CETP (cholesteryl ester transfer protein) activity, but effects of weight loss are not clear. In addition, associations with visceral and subcutaneous adipose tissue are not known. We therefore investigated effects of diet-induced weight loss on HDL-mediated cholesterol efflux and cholesterol ester (CE) transfer in abdominally obese men. Differences between normal-weight and abdominally obese men were also examined. Twenty-five apparently healthy, normal-weight men (waist circumference: <94 cm) and 52 abdominally obese men (waist circumference: 102-110 cm) were included. Abdominally obese subjects were randomly allocated to a dietary weight-loss intervention group or a no-weight loss control group. Individuals from the intervention group followed a very-low-calorie diet for 6 weeks to obtain a waist circumference below 102 cm, followed by a 2-week weight-stable period. Cholesterol efflux was measured in BODIPY-labeled murine J774 macrophages. CE transfer was measured by quantifying the transfer of CE from radiolabeled exogenous HDL to apoB-containing lipoproteins. Cholesterol efflux capacity was 9 percentage point (pp) lower in abdominally obese than in normal-weight men (p≤0.001), while CE transfer was 5 pp higher (p≤0.01). Diet-induced weight-loss of 10.3 kg did not change cholesterol efflux and CE transfer. In addition, stepwise regression analysis did not suggest that the different fat depots are differently related to efflux capacity and CE transfer. After a 2-week weight-stable period, dietary weight loss of 10 kg did not improve ABCA1-mediated cholesterol efflux and CE transfer in abdominally obese men. Show less