Recent Advances on the Antiatherogenic Effects of HDL-Derived Proteins and Mimetic Peptides

Abstract

The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely correlated with the risk of atherosclerosis and cardiovascular disease (CVD) in humans. One of the major mechanisms whereby HDL particles protect against atherosclerosis is that of reverse cholesterol transport from atherosclerotic lesion macrophages to the liver. HDL particles also exhibit various antiatherogenic and cardioprotective effects by modulating the function of various cells including the cells of the artery wall and by expressing antioxidant, anti-inflammatory, antithrombotic and antiapoptotic effects. Most these effects are mediated by various lipid and protein HDL components. A plethora of studies have been conducted in order to shed light on the mechanisms by which each HDL component contributes to the functionality of this lipoprotein. The complete elucidation of these mechanisms will significantly contribute to current efforts focused on the development of therapeutic strategies to promote the antiatherogenic potency of HDL. The present review discusses current knowledge on the biological activities of the major apolipoproteins and enzymes associated with HDL, which may significantly contribute to the overall antiatherogenic and cardioprotective effects of this lipoprotein.

HDL-Related Mechanisms of Olive Oil Protection in Cardiovascular Disease

“…For example, HDL enriched with APOA1, APOA4, or APOM are considered antiatherogenic [37][38][39], whereas HDL-APOA2 and HDL-APOJ are associated with pro-atherogenic effects [39,40]. Thus, the HDL-C concentration per se may not adequately reflect the consequences of alterations in protein composition Fig.…”

HDL-C: Does it matter? An update on novel HDL-directed pharmaco-therapeutic strategies

“…Because the essential function of HDL occurs in the extravascular space, and not in the plasma compartment, it is likely that plasma HDL-C levels have a limited power to predict RCT functionality in the target tissue. Moreover, HDL influences the atherogenic process not only through cholesterol extraction but also through anti-inflammatory and antioxidant properties (25).…”

High-density lipoprotein therapeutics and cardiovascular prevention

“…Moreover, HDL influences the atherogenic process not only through cholesterol extraction but also through antiinflammatory and antioxidant properties. 24 In other words, HDL should be present in high concentration in the arterial lesion to produce the desired effects on LDL oxidation (causing reduced plaque progression), on inflammation (causing plaque stabilization), and on cholesterol exit (causing plaque regression).…”

“…Use of oral or injectable apoAI mimetics. 24,85,86 These short peptides, mimicking functional stretches of apoAI, are postulated to associate with plasma HDL and increase its anti-inflammatory and antioxidant power. This intervention is not expected to increase HDL-C levels.…”