Inability of HDL from abdominally obese subjects to counteract the inhibitory effect of oxidized LDL on vasorelaxation.
Abdominal obesity is associated with a decreased plasma concentration of HDL cholesterol and with qualitative modifications of HDL, such as triglyceride enrichment. Our aim was to determine, in isolated aorta rings, whether HDL from obese subjects can counteract the inhibitory effect of oxidized low density lipoprotein (OxLDL) on endothelium-dependent vasodilation as efficiently as HDL from normolipidemic, lean subjects. Plasma triglycerides were 74% higher (P < 0.005) in obese subjects compared with controls, and apolipoprotein A-I (apoA-I) and HDL cholesterol concentrations were 12% and 17% lower (P < 0.05), respectively. HDL from control subjects significantly reduced the inhibitory effect of OxLDL on vasodilation [maximal relaxation (E(max)) = 82.1 +/- 8.6% vs. 54.1 +/- 8.1%; P < 0.0001], but HDL from obese subjects had no effect (E(max) = 47.2 +/- 12.5% vs. 54.1 +/- 8.1%; NS). In HDL from abdominally obese subjects compared with HDL from controls, the apoA-I content was 12% lower (P < 0.05) and the triglyceride-to-cholesteryl ester ratio was 36% higher (P = 0.08)). E(max)(OxLDL + HDL) was correlated with HDL apoA-I content and triglyceride-to-cholesteryl ester ratio (r = 0.36 and r = -0.38, respectively; P < 0.05). We conclude that in abdominally obese subjects, the ability of HDL to counteract the inhibitory effect of OxLDL on vascular relaxation is impaired. This could contribute to the increased cardiovascular risk observed in these subjects.
Perségol
Laurence
L
Institut National de la Santé et de la Recherche Médicale U866, Dijon F-21000, France.
Vergès
Bruno
B
Gambert
Philippe
P
Duvillard
Laurence
L
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D011817:Rabbits; D014280:Triglycerides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D000109:Acetylcholine