In a prototypic HDL particle, 2 to 5 molecules of apoA-I and ≈100 molecules of phosphatidylcholine form an amphipathic shell in which several molecules of unesterified cholesterol are imbedded surrounding a core of completely water-insoluble cholesterol esters. However, although not disputed, such a conclusion neglects the structural and functional heterogeneity of HDL, which is neither reflected by the nonfunctional clinical biomarker HDL-C nor has yet been targeted by randomized controlled trials 7 – 10 or Mendelian randomization studies. In fact, it has been argued that low HDL-C may only represent a marker for proatherogenic risk factors, rather than HDL being a mediator protecting against atherogenesis. 11 – 13 Thus, the pathogenic role and, hence, suitability of HDL as a therapeutic target has increasingly been questioned. 7 – 10 Moreover, in several inborn errors of human HDL metabolism and genetic mouse models with altered HDL metabolism, the changes in HDL-C levels were not associated with accompanying changes in cardiovascular risk or atherosclerotic plaque load, respectively, as has been expected from epidemiological studies. Unfortunately, it has been proven difficult to reduce coronary risk with drugs increasing HDL-C, such as fibrates, niacin, or inhibitors of cholesteryl ester transfer protein (CETP), beyond that achieved with statin therapy alone. In line with a causally protective effect, HDL can exert a broad spectrum of antiatherogenic effects capable of halting or even reversing atherosclerosis in several animal models, in particular by transgenic overexpression or exogenous application of apolipoprotein A-I (apoA-I), the most abundant protein of HDL. Furthermore, HDL is being intensely investigated as a potential therapeutic target in patients at high cardiovascular risk. 5 Accordingly, the metabolism and the vascular effects of HDL have attracted enormous interest. 1 – 4 Of note, in patients fully treated according to current guidelines with intense statin therapy and low-density lipoprotein cholesterol (LDL-C) at target levels, HDL-C remains predictive of outcome for major adverse cardiovascular events. In population studies, high-density lipoprotein cholesterol (HDL-C) is inversely related to the risk of myocardial infarction and death. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
0 kommentar(er)
