High-density lipoproteins: an emerging target in the prevention of cardiovascular disease

Abstract

High-density lipoproteins (HDLs) have been well established to protect against the development of atherosclerotic cardiovascular disease. It has become apparent that in addition to the promotion of reverse cholesterol transport, HDLs possess a number of additional functional properties that may contribute to their beneficial influence on the arterial wall. A number of exciting therapeutic strategies have been developed that target HDL and its ability to protect against the development of atherosclerotic plaque. This paper will review how the promotion of the functional properties of HDL inhibits the formation of atherosclerotic plaque and stabilises lesions in patients with established disease.

HDLs activate ADAM17‐dependent shedding

“…Because of the beneficial influence of HDLs on the vascular wall, we attend to the emergence of therapeutic strategies aiming at increasing HDLs for the prevention of cardiovascular diseases (Cutri et al, 2006). We have described for the first time that HDLs stimulate ADAM17 substrate shedding and because of the extremely large diversity of ADAM17 substrates (Smalley and Ley, 2005) it is of interest to investigate the impact of higher levels of HDLs on cellular function that could be altered by the shedding of ADAM17 substrates.…”

“…The second mechanism involves membrane proteins like the ATP binding cassette transporter (ABC) A1 (Wang and Tall, 2003), which accelerates cholesterol export to lipid-poor apoA1 to form nascent HDLs, whereas ABCG1 (Wang et al, 2004) and scavenger receptor BI ( Ji et al, 1997) accelerate cholesterol transfer to HDLs. In addition to their role in reverse-cholesterol transport, HDLs also have antioxidant (Navab et al, 2000;Ou et al, 2003;Nicholls et al, 2005), anti-inflammatory (Navab et al, 2005), and antithrombotic (Rosenson and Lowe, 1998) properties that play an important role in their antiatherogenic effects (Barter and Rye, 2006;Choi et al, 2006;Cutri et al, 2006). It is thought that cholesterol is non-randomly distributed within the membrane, participating in the generation of lipid domains rich in cholesterol and sphingolipids, called lipid rafts (Brown, 1998;Simons and Vaz, 2004).…”

To Establish the Reference Intervals of Lipid Profile in Punjab

“…In clinical chemistry, the use of the term lipids generally refers to lipoprotein metabolism and atherosclerosis, a cause of coronary heart disease (CHD) [2]. Available global data have clearly established the relationship of lipids and other risk factors with cardiovascular and cerebrovascular events [3][4][5][6][7][8][9][10][11]. It is therefore essential to establish a reference range of the values of serum lipids for a given population as only a few studies have been carried out in other regions of India [12][13][14][15].…”

Type 2 Diabetes and Cardiovascular Disease: Reducing the Risk

“…The study showed that for every 5 mg/dL increase in HDL-C level, there was a 26% reduction in CVD risk. 59 Emerging evidence continues to show the antiatherosclerotic properties of HDL-C. 60 In addition to its pivotal role in reverse cholesterol transport, HDL-C enhances NO bioavailability and has potential anti-inflammatory, antithrombotic, antioxidant, and antiapoptotic properties. As a result of researchers improving their knowledge of factors that promote HDL-C levels and its function, new drug therapies (e.g., more potent PPAR agonists) are in development.…”

“…As a result of researchers improving their knowledge of factors that promote HDL-C levels and its function, new drug therapies (e.g., more potent PPAR agonists) are in development. 60 Since patients with T2DM often exhibit mixed dyslipidemia, multiple agents may be required to reach treatment goals. However, there is an increased risk of adverse drug events (ADEs) when higher doses are used and/or certain antihyperlipidemic agents are combined (e.g., rhabdomyolysis when combining statins and fibrates) are combined.…”