Abstract 375: Calcification of Human Saphenous Vein Correlates With Endothelial Dysfunction: A Histopathophysiological and Morphological Study

Abstract

Background: Endothelial dysfunction decreases nitric oxide, which leads to the development of intimal hyperplasia and, eventually, vein graft failure. Failed vein grafts have been found to have calcium deposits, enlarged intima, atherosclerotic plaques, and extracellular matrix deposition. This project examined the effect of calcification on endothelial function by measuring the endothelial relaxation and the expression of nitric oxide synthase (eNOS) in saphenous veins. Methods: Freshly collected HSV (58) samples from CABG patients were equilibrated in a muscle bath and phenylephrine-induced contraction and carbachol-induced relaxation (endothelium-dependent) were measured. Vein sections were stained using Verhoeff-Van Gieson (VVG), Movat, and Von Kossa stains. Endothelial coverage was determined by eNOS, and Lectin staining. Calcification, intimal and medial basal thickness, endothelial coverage, and extracellular matrix deposition data were quantified using light microscopy and digital image analysis. Results: Of the 58 veins analyzed, 17 displayed calcification. The average basal intimal thickness of the samples was 65.44 ± 7.99 μm. Presence of calcification in HSV correlated with higher intimal basal thickness (p=0.0092, n=46, panel A), lower endothelial relaxation (p=0.032, n=43, panel B), loss of eNOS expression (p=0.0397, n=29), loss of endothelial coverage (p=0.0178, n=29), and increased extracellular matrix deposition (p=0.0180, n=22, panel C). Conclusions: Calcified veins displayed lowered endothelial relaxation, higher intimal basal thickness, reduced endothelial coverage, reduced eNOS expression, and increased extracellular matrix deposition. Calcification was associated with factors that contribute to intimal hyperplasia formation and vein graft failure.