HDL-Raising Therapies – Target Pipeline List 01/2019
Targets: high density lipoprotein, HDL; apolipoprotein A-I, apoA-I; ApoC-III; apoE; lecithin: cholesterol acyl-transferase, LCAT; ATP-binding cassette A1 (ABCA1) transporter; cholesteryl ester transfer protein, CETP; P2Y13 receptor
This Target Pipeline List provides an overview of biologic and small molecule approaches to raise high density lipoprotein (HDL) for reduction of recurrent cardiovascular events.
Studies have shown that low levels of HDL are associated with increased progression of atherosclerosis and risk of cardiovascular disease. Data from the Framingham Heart Study have shown that subjects with the highest HDL levels exhibit the lowest risk of developing coronary heart disease (CHD). Observational studies have consistently demonstrated that high serum levels of HDL are associated with reduced risk for CHD development and related complications such as myocardial infarction, stroke, and death, whereas low serum levels of this lipoprotein are correlated with increased risk for cardiovascular morbidity and mortality in both men and women. The positive effects of HDL and its negative correlation with heart disease are thought to be mainly due to its primary role in reverse cholesterol transport.
Reverse cholesterol transport is a pathway by which cholesterol is transported from the artery walls to the liver for excretion from the body. Although the concept of reverse cholesterol transport from macrophages to liver and ultimately biliary excretion is the most popular mechanism to explain the ability of HDL to inhibit atherosclerosis, many other properties of HDL have been demonstrated in vitro that could contribute to its antiatherogenic effects. HDL has been reported to exert various atheroprotective properties, including anti-apoptotic effects, anti-inflammatory effects and cholesterol efflux capacity.
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