Metabolic syndrome aggravates the increased endothelial activation and low-grade inflammation in subjects with familial low HDL.
ABSTRACT Inhibition of cytokine-induced expression of adhesion molecules is one of the atheroprotective mechanisms of high-density lipoprotein (HDL).
We investigated whether increased endothelial activation and low-grade inflammation are present in Finnish subjects with familial low HDL, and which factors contribute to the inflammatory parameters.
High-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were measured in 91 subjects with low HDL-cholesterol from 41 low-HDL families and in 112 normolipidemic controls with comparable age- and gender distribution. Presence of the features of the metabolic syndrome (MetS) was recorded.
sVCAM-1, sICAM-1, sE-selectin, and hsCRP were significantly higher in low-HDL subjects than in the controls (sVCAM-1: 560+/-147 ng/mL versus 496+/-95 ng/mL, P = 0.001; sICAM-1: 247+/-60 ng/mL versus 215+/-47 ng/mL, P<0.001; sE-selectin: 52+/-20 ng/mL versus 44+/-16 ng/mL, P = 0.022; and hsCRP: 1.73+/-2.05 mg/L versus 0.85+/-1.10 mg/L, P<0.001). Low-HDL subjects had increased body mass index (BMI) and waist, and elevated insulin and triglyceride levels. Adhesion molecules and hsCRP increased according to the number of the features of the MetS.
The presence of the MetS in subjects with familial low HDL-cholesterol aggravates the low-grade inflammation and endothelial activation, and ultimately may add to the higher susceptibility for atherosclerotic disease in these individuals.
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ABSTRACT: High density lipoprotein (HDL) has many properties, which contribute to its atheroprotective role. However, some recent clinical trials have identified subjects with the progression of atherosclerosis despite normal levels of HDL cholesterol. This raises the question if all subfractions of HDL have the same properties. Moreover, recent investigations have shown that both acute and chronic inflammation may lead to structural and functional changes of HDL, which render the particles proinflammatory. Although therapeutic agents that increase HDL levels are now quite well established it is not clear whether they influence HDL quality. We review the current state of knowledge on the properties of HDL and factors/therapeutic agents which may restrain the transformation of normal HDL into dysfunctional HDL.Progress in lipid research 05/2012; 51(4):314-24. · 10.67 Impact Factor
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ABSTRACT: To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases. Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects. Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preβ1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels. The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.Lipids in Health and Disease 01/2011; 10:17. · 2.02 Impact Factor
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ABSTRACT: ATP-binding cassette transporter A1 (ABCA1) is an integral cell membrane protein that protects cardiovascular disease by at least two mechanisms: by export of excess cholesterol from cells and by suppression of inflammation. ABCA1 exports cholesterol and phospholipids from cells by multiple steps that involve forming cell surface lipid domains, binding of apolipoproteins to ABCA1, activating signaling pathways, and solubilizing these lipids by apolipoproteins. ABCA1 executes its anti-inflammatory effect by modifying cell membrane lipid rafts and directly activating signaling pathways. The interaction of apolipoproteins with ABCA1 activates multiple signaling pathways, including Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3), protein kinase A, Rho family G protein CDC42 and protein kinase C. Activating protein kinase A and Rho family G protein CDC42 regulates ABCA1-mediated lipid efflux, activating PKC stabilizes ABCA1 protein, and activating JAK2/STAT3 regulates both ABCA1-mediated lipid efflux and anti-inflammation. Thus, ABCA1 behaves both as a lipid exporter and a signaling receptor. Targeting ABCA1 receptor-like property using agonists for ABCA1 protein could become a promising new therapeutic target for increasing ABCA1 function and treating cardiovascular disease. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).Biochimica et Biophysica Acta 09/2011; 1821(3):522-9. · 4.66 Impact Factor