Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine

Abstract

Introduction: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. Methods: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D–deficient diet, (2) vitamin D–sufficient diet, and (3) vitamin D–supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. Results: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D–deficient compared with vitamin D–sufficient or vitamin D–supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D–deficient swine compared with the vitamin D–sufficient or vitamin D–supplemented animal groups. Conclusions: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.