Cardioprotective functions of HDLs

Abstract

This article is available online at http://www.jlr.org inverse predictors of the risk of having a cardiovascular event ( 1-5 ); moreover, a low concentration of HDL cholesterol remains predictive of increased cardiovascular risk, even when low density lipoprotein (LDL) cholesterol has been reduced to very low levels by treatment with statins ( 6 ); ii ) HDLs have several well-documented functions with the potential to protect against cardiovascular disease ( 7,8 ); iii ) interventions that increase the concentration of HDLs inhibit the development and progression of atherosclerosis in several animal models ( 9-12 ); and iv ) in "proofof-concept" studies in humans, intravenous infusions of reconstituted HDLs (rHDLs) consisting of apoA-I complexed with phospholipids promote regression of coronary atheroma as assessed by intravascular ultrasound ( 13,14 ).However, interventions that increase the concentration of HDL cholesterol in humans have not yet been shown to translate into a reduction in clinical cardiovascular events. Indeed, recent human clinical trials investigating the effects of raising the level of HDL cholesterol by treatment with cholesteryl ester transfer protein (CETP) inhibitors or with niacin failed to demonstrate any clinical cardiovascular benefi t ( 15-17 ) (http://www.thrivestudy. org), and in one case, the treatment caused harm ( 15 ). A reasonable assumption that has been made from these studies is that the cholesterol content of HDLs is not the factor that protects. Thus, if HDLs do have direct cardioprotective properties, it follows from the human population studies that, while the concentration of HDL cholesterol is generally an excellent marker of the HDL functions that do protect, it does not invariably refl ect their cardioprotective functions. This is consistent with the fi nding in a recent Mendelian randomization study that some genetic mechanisms that raise the concentration of HDL cholesterol appear not to lower the risk of myocardial infarction ( 18 ). The authors of this analysis concluded that, while The proposition that high density lipoproteins (HDLs) protect against the development of cardiovascular diseases is based on a number of robust and consistent observations: i ) numerous human population studies have shown that the plasma concentrations of both HDL cholesterol and the major HDL apolipoprotein, apoA-I, are independent, Abbreviations: CETP, cholesteryl ester transfer protein; HO-1, heme oxygenase-1; PON-1, paraoxonase-1; rHDL, reconstituted HDL; SR-B1, scavenger receptor-B1; VCAM-1, vascular cell adhesion molecule-1.

Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia

“…1 In this circumstance, HDL-C has attracted attention because it has several welldocumented functions to protect against CVD. 25 HDL also inhibit vascular inflammation and oxidative modification of LDL. Thus, HDL-C exerts a beneficial role in vascular health, particularly in endothelial function.…”

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

“…The major mechanism by which HDL is thought to exert its cardio-protective effects is by removing cholesterol from the artery wall through a process referred to as reverse cholesterol transport, involving the interaction of apolipoprotein A-I with ATP-binding cassette transporters ABCA1 and ABCG1 [72]. Further, HDL and its subpopulations have anti-oxidative, antiinflammatory, cytoprotective, vasodilatory, and antithrombotic activities, all of which may slow or prevent the development of atherosclerosis [73]. One of MPO's putative contributions to atherosclerosis involves sitespecific oxidative modification of HDL, thereby attenuating its anti-atherogenic properties.…”

Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties

“…19 Hence, it is assumed that the cardioprotective effects of HDL are largely based on its ability to remove cholesterol from macrophages, which represents the first and crucial step of reverse cholesterol transport. 20 In recent years, it has become evident that the atheroprotective, anti-inflammatory, and antioxidative effects of HDL are critically dependent on its protein cargo [21][22][23][24] because HDLassociated proteins were found to be involved in many biologic functions apart from lipid metabolism, such as regulation of inflammation and immune responsiveness. 15 We and others have shown that qualitative alterations of HDL in CKD and ESRD result in dysfunctional properties, transforming HDL from a protective to a deleterious particle.…”