Abstract 1344: Restoration of Endothelial Function After Infusion of Reconstituted High-Density Lipoprotein in Subjects with Type 2 Diabetes Mellitus
Background Patients with type 2 diabetes mellitus (DM2) are characterized by dyslipidemia and endothelial dysfunction as well as high risk for cardiovascular disease. Unfortunately, statin-induced LDL lowering has been shown to be insufficient to restore vascular dysfunction in these patients. In the present study, we investigated what the value of HDL-increasing strategies could be for improving endothelial function in DM2.
Methods In 7 uncomplicated DM2 and 7 normolipidemic controls, endothelial function was assessed by venous occlusion plethysmography. Forearm blood flow (FBF) responses to intra-arterial infusion of cumulative doses of the endothelium-dependent and independent vasodilators serotonin (5HT) and sodium nitroprusside, respectively and the inhibitor of nitric oxide synthase NG-monomethyl-l-arginine (L-NMMA) were measured. Subsequently, HDL-c was increased by systemic infusion of apolipoprotein A-I/phosphatidylcholine disks (rHDL) at a dose of 80mg/kg during a 4-hour period. Thereafter measurements of basal and stimulated NO activity as well as endothelium-independent vasodilation were repeated. Plasma levels of ApoA1 and oxLDL were assessed before and 4 hours after rHDL infusion.
Results At baseline, HDLc levels in DM2 were comparable to control subjects (1.1 ± 0.2 vs. 1.2 ± 0.3 mmol/L, ns). 5HT-induced vasodilation (max 17±10%) and L-NMMA induced vasoconstriction (max −17±15%) were clearly blunted in DM2 versus controls (5-HT 114±22 and L-NMMA −48±5%, both p<0.05). rHDL infusion induced a rise in ApoA1 plasma levels (1.2 ± 0.2 to 2.8 ± 0.4 vs. 1.2 ± 0.2 to 2.7 ± 0.4 g/L, p<0.01) and decreased oxLDL levels (127±36 to 106±35 vs. 47±10 to 40±78 U/L, p<0.05) in DM2 and controls respectively. rHDL restored FBF responses to 5HT (86±22%, p<0.05) and L-NMMA (−45±9%, p<0.01) in DM2. No effect of rHDL on vasomotion was observed in control subjects.
Conclusions We show that rHDL/apoAI increase in DM2 is associated with restoration of both basal and stimulated NO bio-availability. Strikingly, rHDL also decreased oxLDL levels in both DM2 and controls. The data suggest that rHDL can exert direct beneficial effects on the arterial wall in DM2 and lend support for therapeutic strategies that increase the vasodilatory properties of HDL.