[Atherogenic dyslipidemia and the metabolic syndrome: pathophysiological mechanisms].
Atherogenic dyslipidemia (ADL), a frequent metabolic derangement found in patients with manifest atherosclerosis, is characterized by hypertriglyceridemia, low plasma HDL cholesterol and prevalence of small dense LDL particles. The key pathogenetic mechanisms of ADL are closely linked to insulin resistance, the lack of appropriate responses to insulin in peripheral cells, especially in adipose tissue, skeletal muscles and liver. Impaired insulin signalling leads to a decreased suppression of lipolysis, defective fat storage in adipocytes, and increased flux of free fatty acids to the liver, which together with posttranslational stabilization of apolipoprotein B enhances the assembly and secretion of VLDL particles. Decreased activity of lipoprotein lipase contributes to slow clearance of triglyceride-rich particles, with negative consequences in LDL metabolism. Impaired HDL synthesis, intravascular remodelling, and catabolism decreases reverse cholesterol transport from peripheral tissues, hepatocytes and macrophages. Small dense LDL particles are considered to be highly atherogenic, due to increased penetration of arterial intima, and decreased antioxidant capacity. Better understanding of pathophysiological mechanisms involved in ADL could promote new therapeutic methods, as well as increase the compliance with essential lifestyle interventions.
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IV interní klinika 1, LF UK a VFN U Nemocnice 2, 128 08 Praha. azak@vfn.cz
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D050197:Atherosclerosis / Q000150:complications* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D050171:Dyslipidemias / Q000150:complications* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000150:complications / Q000378:metabolism; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism
D008076:Cholesterol, HDL; D005227:Fatty Acids; D002784:Cholesterol