Single LDL Apheresis Improves Endothelium-Dependent Vasodilatation in Hypercholesterolemic Humans

Abstract

BACKGROUND: Although long-term lipid-lowering therapy improves endothelium-dependent vasodilatation in humans, it remains unknown whether the short-term removal of LDL per se ameliorates endothelial dysfunction. METHODS AND RESULTS: To examine the effects of a single session of LDL apheresis on endothelial function in patients with hypercholesterolemia, we measured forearm blood flow (FBF) by strain-gauge plethysmography before and after single LDL apheresis while infusing acetylcholine (ACh; 4 to 24 micrograms/min) and sodium nitroprusside (SNP; 0.2 to 1.2 micrograms/min). The single session of LDL apheresis reduced total LDL (from 142.2 +/- 15.0 to 32.6 +/- 5.0 mg/mL, P < .0005) and oxidized LDL (from 111.6 +/- 22.8 to 30.0 +/- 5.4 ng/mL, P < .005). Although ACh and SNP increased FBF dose-dependently before and after LDL apheresis, the endothelium-dependent vasodilatation responses to ACh were significantly augmented (P < .01) after the single session of LDL apheresis without changes in the endothelium-independent vasodilatation responses to SNP. The plasma levels of total and oxidized LDL correlated with the degree of ACh-induced vasodilatation. Furthermore, the local production of nitrate/nitrite, metabolites of NO, during ACh infusion was significantly (P < .05) augmented by LDL apheresis, and there was a significant correlation between the degree of ACh-induced vasodilatation and the production in nitrate/nitrite (r = .99, P < .0005). CONCLUSIONS: We demonstrated that even a single session of LDL apheresis with the reduction of total LDL and oxidized LDL improved endothelial function. Our results suggest that total LDL and/or oxidized LDL may directly impair endothelial function in the human forearm vessel.