Browsing by Subject "Lipoproteins, HDL"

Now showing 1 - 8 of 8
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    Familial disorders of low HDL
    (1989-03-23) Hobbs, Helen H.
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    HDL Phospholipid and ABCA1-Mediated Cholesterol Efflux Are Reduced in Patients with Very High HDL-C Who Develop Early Coronary Artery Disease
    (2014-04-15) Agarwala, Anandita; Khera, Amit; Hobbs, Helen H.; Grundy, Scott M.
    BACKGROUND: Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with apparent ‘protection’ from CAD. OBJECTIVE: We identified a number of individuals with high HDL-C levels who develop CAD, a paradoxical phenotype and hypothesized that such individuals may have HDL with altered structure and function, and compared controls with similarly high HDL-C and no coronary disease. METHODS: 55 subjects with HDL-C above the 90th percentile, early CAD, and no major known risk factors for coronary disease were identified. We selected 120 controls without CAD, each matched for race, gender, and HDL-C level. RESULTS: Comparison of HDL particle characteristics between cases and controls demonstrated a significant reduction in HDL phospholipid composition and cholesterol efflux capacity in cases as compared to controls. CONCLUSION: Reduced cholesterol efflux capacity in cases with elevated HDL-C and CAD may explain the development of early coronary artery disease. Cholesterol efflux capacity may in fact be a better predictor of the risk of coronary disease then HDL-C levels alone. The reduction in HDL phospholipid in the cases may help account for impaired cholesterol efflux.
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    Impaired Cholesterol Efflux Capacity May Help Explain Development of Early Coronary Artery Disease in Subjects with Very High HDL-C
    (2014-02-04) Agarwala, Anandita; Rodrigues, Amrith; Trinidade, Kevin; Risman, Marjorie; Qu, Liming; Cuchel, Marina; Billheimer, Jeffrey; Rader, Daniel J.
    Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with apparent 'protection' from CAD. A minority of individuals with very high HDL-C levels also develops CAD, a paradoxical phenotype. We hypothesize that such individuals may have HDL with altered structure and/ or function, and compared these individuals (cases) to individuals with very high HDL-C without CAD (controls). We identified 55 subjects with HDL-C above the 90th percentile, early CAD, and no major risk factors for coronary disease. We selected 120 controls without CAD, each matched for race, gender, and HDL-C level. Controls were selected to be the same age or no more than 10 years older than the cases. Studies to assess HDL composition and size distribution, cholesterol efflux capacity, and lecithin-cholesterol acyltransferase (LCAT) activity in cases and controls were conducted. Comparison of HDL particle characteristics between cases and controls demonstrated a significant reduction in HDL phospholipid composition between cases and controls (92 ± 37 mg/dl vs. 109 ± 43 mg/dL, p value 0.0095). The mean plasma total cholesterol efflux capacity was significantly reduced in subjects with elevated HDL-C and CAD as compared to controls (1.96 ± 0.39 % efflux/ 2hr/ 1% plasma vs. 2.11 ± 0.43 % efflux/ 2hr/ 1% plasma, p value 0.040). The reduction became even more significant when looking at mean ABCA1- selective cholesterol efflux between cases and controls 0.60 ± 0.24 % efflux/ 2hr/ 1% plasma vs. 0.71 ± 0.32 % efflux/ 2hr/ 1% plasma, p value 0.033). Furthermore, there was a significant reduction in mean efflux per HDL particle in cases as compared to controls (0.023 ± 0.005 % efflux/ 2hr/ 1% plasma vs. 0.025 ± 0.006 % efflux/ 2hr/ 1% plasma, p value 0.029). No significant difference was observed between cases and controls in HDL particle size or plasma LCAT activity. Reduced cholesterol efflux capacity in cases with elevated HDL-C and CAD may explain the development of early coronary artery disease. This finding reinforces the belief that cholesterol efflux capacity may in fact be a better predictor of the risk of coronary disease then HDL-C levels alone. Furthermore, the reduction in HDL phospholipid in the cases may help account for impaired cholesterol efflux.
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    Molecular Basis of HDL-Mediated Endothelial Cell Migration and Reendothelialization
    (2005-12-20) Seetharam, Divya; Shaul, Philip W.
    Vascular disease risk is inversely related to circulating levels of high density lipoprotein (HDL) cholesterol. The atheroprotective nature of HDL is attributed mainly to its role in reverse cholesterol transport (RCT). However, recent reports of human and animal studies have suggested that the atheroprotective nature of HDL is not sufficiently explained by RCT. Therefore, the mechanisms by which HDL provides vascular protection are unclear. The disruption of endothelial monolayer integrity is an important contributing factor in multiple vascular disorders, and vascular lesion severity is tempered by enhanced endothelial repair. In these studies we show that HDL stimulates endothelial cell migration in vitro in a nitric oxide-independent manner via scavenger receptor B type I (SR-BI)-mediated activation of Rac GTPase. This process does not require HDL cargo molecules, and it is dependent on the activation of Src kinases, phosphatidylinositol 3-kinase, and p44/42 mitogen-activated protein kinases. Rapid initial stimulation of lamellipodia formation by HDL via SR-BI, Src kinases and Rac is also demonstrable. Paralleling the in vitro findings, carotid artery reendothelialization following perivascular electric injury is blunted in apolipoprotein A-I null (apoA-I-/-) mice, and reconstitution of apoA-I expression rescues normal reendothelialization. Furthermore, reendothelialization is impaired in SR-BI-/- mice. Thus, HDL stimulates endothelial cell migration via SR-BI-initiated activation of Rac GTPase, and HDL and SR-BI promote reendothelialization in vivo, revealing that signaling by the HDL-SR-BI tandem has a potent beneficial impact on the cardiovascular system.
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