Dysfunctional HDL as a Therapeutic Target for Atherosclerosis Prevention

Abstract

Hypercholesterolemia is one of the main risk factors for the development of atherosclerosis. Among the various lipoprotein classes, however, high density lipoproteins (HDL) are inversely associated with the incidence of atherosclerosis, since they are able to exert a series of atheroprotective functions. The central role of HDL within the reverse cholesterol transport, their antioxidant and anti-inflammatory properties and their ability to preserve endothelial homeostasis are likely responsible for HDL-mediated atheroprotection. However, drugs that effectively raise HDL-C failed to result in a decreased incidence of cardiovascular event, suggesting that plasma levels of HDL-C and HDL function are not always related. Several evidences are showing that different pathologic conditions, especially those associated with an inflammatory response, can cause dramatic alterations of HDL protein and lipid cargo resulting in HDL dysfunction. Established and investigational drugs designed to affect lipid metabolism and to increase HDL-C are only partly effective in correcting HDL dysfunction.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

“…HDL particles are recognized as a protective factor against cardiovascular disease since they promote several atheroprotective functions [ 3 ] and their increment by 1 mg/dL is linked to an average decrease of 3% in the risk for development of CVD [ 4 , 5 ]. During inflammation in acute phase or in chronic situations (e.g., different dysmetabolic diseases), HDLs undergo significant remodeling in their lipid as well as in their proteome content [ 6 – 10 ], resulting in impaired functions that lead to CVD [ 11 ]. Proatherogenic HDL dysfunctionality may include reduced antioxidation function [ 12 – 14 ]‚ impaired cholesterol efflux [ 7 , 15 ], and reduced nitric oxide production [ 16 ].…”

HDL Inhibited Atherosclerosis Induced by Radiation Injury

“…Notwithstanding ionizing radiation even in low doses will aggravate the risk of cardiovascular disease, primarily causing endothelial cell damage which leads to the process of atherosclerosis [20,21]. HDL reduces the deposition of cholesterol into tissues thereby playing an anti-atherosclerotic role by preventing the occurrence and development of atherosclerosis [22]. Our clinical studies demonstrated that radiation exposure remained a high-risk factor for the occurrence of atherosclerosis however HDL could effectively reduce such risk.…”

HDL Inhibited Atherosclerosis Induced by Radiation Injury

“…Although some studies suggested that moderate ultraviolet radiation can prevent cardiovascular disease [19]. Low dose of ionizing radiation will increase the risk of cardiovascular disease, mainly cause endothelial cell damage and participate in the process of atherosclerosis [20,21].HDL plays an anti atherosclerotic role by reducing the deposition of cholesterol in tissues, thus limiting the occurrence and development of atherosclerosis [22].Our clinic studies showed that radiation exposure was high risk factor during atherosclerosis prevalence, HDL superior to reduce this risk. Radiation can induce apoptosis through oxidative stress, during the cell experiment, MAECs apoptosis increased and HDL may protect [23].…”