Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level

Abstract

ObjectiveThe potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD.MethodsHDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum.ResultsWhile cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (p<0.001). The efflux to HDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, p<0.001 for both). The efflux to HDL2 was reduced in men with early CHD (p<0.01) only in conjunction with their low HDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, p<0.001). A low ratio of HDL2 to total HDL was associated with MetS (p<0.001).ConclusionOur results indicate that impaired efflux to HDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed.

Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

“…The five subfractions of HDL are HDL2a, HDL2b, HDL3a, HDL3b, and HDL3c, according to their physicochemical composition, which indicates their atheroprotective role. Subjects with metabolic syndrome and early cardiovascular heart diseases (CHD) show a low cholesterol efflux by HDL2 and HDL3 within low levels in plasma of these subclasses [ 15 , 16 ]. In subjects with diabetes, HDL2 may be associated with a decrease of carotid artery intima-media thickness [ 17 ].…”

“…However, other meta-analyses showed that the increase in HDL-C or HDL-P (HDL particles) via pharmacological manipulation in secondary prevention is not beneficial in randomized clinical trials including 26,858 participants with a follow-up period of 1–6.2 years [ 41 ]. Subjects with metabolic syndrome and early cardiovascular heart diseases (CHD) show low cholesterol efflux by HDL2 and HDL3 within low levels in plasma of these subclasses [ 15 , 16 ]. In subjects with diabetes, HDL2 may decrease carotid artery intima-media thickness [ 17 ].…”

Clinical and serum lipid profiles and LDLR genetic analysis of xanthelasma palpebrarum with nonfamilial hypercholesterolemia

“…The prevalence of carotid atherosclerosis was also significantly higher than the control group. As we known, HDL is an anti‐atherosclerotic plasma lipoprotein, a protective factor for coronary heart disease, also known as the “lipid scavenger of blood vessel.”17,18 However, recent studies have found that high‐level HDL can cause damage to peripheral tissues and organs, vascular system, increase the prevalence of atherosclerosis, heart disease, tumors, and even increase the risk of death . 19,20 These results support too high‐level HDL is a risk factor, which might contribute to pathogenesis of XP.…”

Distinct Fatty Acid Compositions of HDL Phospholipids Are Characteristic of Metabolic Syndrome and Premature Coronary Heart Disease—Family Study

“…The study population ( n = 112, Table 1 ) consisted of Northern Finnish families ( n = 24), all of which included a proband with premature CHD and low HDL-C as described earlier [ 47 ]. The inclusion criteria for probands were HDL-C below 1.0 mmol/L, plasma LDL cholesterol level below 4.0 mmol/L, plasma triglyceride level below 3.0 mmol/L, no treatment for diabetes and the first CHD event (acute myocardial infarction, coronary angioplasty or coronary bypass operation) before the age of 60.…”