Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation

OBJECTIVE The object of the present study is to determine whether native (n ) low-density lipoprotein (LDL) isolated from men with type n: diabetes and abnormal endothelial function inhibits endothelium-dependent relaxation mo re than n-LDL isolated from nondiabetic control subjects. BACKGROUND Endothelium-dependent vasodilation is impaired in men with type II diabetes and this may result from qualitative rather than quantitative a bnormalities of LDL. METHODS Forearm blood flow responses to brachial artery infusions of acetyl choline (endothelium-dependent vasodilator) and nitroprusside (endothelium- independent vasodilator) were measured in 10 men with uncomplicated type II diabetes and 10 nondiabetic men of similar age and with similar plasma con centrations of LDL cholesterol. Native LDL was isolated by discontinuous de nsity gradient ultracentrifugation using EDTA to prevent oxidation. Precons tricted rabbit aortic ring bioassay was used to determine inhibitory proper ties of n-LDL on endothelium-dependent relaxation by measuring relaxation t o acetylcholine (and nitroprusside) in the presence and absence of n-LDL. RESULTS Forearm blood flow responses to acetylcholine but not nitroprusside were significantly impaired (p < 0.01) in diabetic men compared with contr ol subjects. Native LDL (10 and 100 mu g protein/ml) from diabetic men inhi bited relaxation to acetylcholine by 13.9 +/- 4.8% and 61.9 +/- 7.8% (mean inhibition for all doses +/- SE), respectively, whereas n-LDL from control subjects inhibited relaxation by 7.3 +/- 3.0% and 23.9 +/- 5.7% (p < 0.01 f or a difference between diabetic and control n-LDL). Relaxation to nitropru sside was not significantly inhibited by n-LDL. CONCUSIONS A qualitative abnormality of LDL may account for endothelial dys function in men with type II diabetes. (C) 2000 by the American College of Cardiology.