The atherogenic lipoprotein phenotype and vascular endothelial dysfunction.
There is accumulating evidence that elevated plasma triglycerides and related abnormalities constitute an independent cardiovascular risk factor. Although the pathogenetic basis for the apparent relationship between elevated triglyceride-rich lipoproteins and CAD is still uncertain, evidence is accumulating to suggest that endothelial dysfunction is involved. There is evidence to suggest that triglyceride-rich particles may be directly damaging to the endothelium; this may be principally via oxidative mechanisms. Triglyceride-rich particles can cross the endothelial barrier and enter the arterial wall, thus placing them in a position to promote direct endothelial damage. These particles stimulate endothelial expression of adhesion molecules and the prothrombotic factor PAI-1. By reducing LDL size and HDL cholesterol concentrations, thereby further increasing the endothelial oxidative burden, triglyceride-rich particles may indirectly promote endothelial dysfunction. In addition, free fatty acids, which are the major substrates for endogenous synthesis of triglyceride-rich particles, are also potentially damaging to the endothelium. This occurs via oxidative stress, by facilitating transfer of LDL across the endothelium, and by enhancing toxicity of triglyceride-rich particles. Finally, there is recent strong evidence to suggest that increased postprandial circulating concentrations of triglyceride-rich particles and remnant particles may be deleterious to the endothelium.
Department of Clinical Biochemistry, Glasgow Royal Infirmary University NHS Trust, UK. nsattar@clinmed.gla.ac.uk
N
N
Sattar
J R
JR
Petrie
A J
AJ
Jaap
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D018384:Oxidative Stress; D014280:Triglycerides / Q000378:metabolism
D008077:Lipoproteins, LDL; D014280:Triglycerides