Yan-hong Guo1, Feng-ying Chen, Gui-song Wang, Li Chen, Wei Gao. 1. Department of Cardiology, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Abstract
BACKGROUND: While hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases, the effect of hyperhomocysteinemia on the vascular adventitia and vessel remodeling has not been clearly demonstrated. We investigated the effect of the hyperhomocysteinemia on adventitial hyperplasia and vascular remodeling following balloon injury in rats and the underlying mechanisms. METHODS: Rats were fed with diet containing methionine for 4 weeks to increase plasma homocysteine before balloon injury. Vascular geometrical changes were assessed at different time points following balloon injury. The collagen deposition was determined by picrosirius red staining and immunohistochemical staining. RESULTS: When compared with normal diet group, moderate hyperhomocysteinemia in methionine diet group significantly exacerbated adventitial hyperplasia at day 7 and collagen deposition mainly in the adventitia at day 28 following balloon injury. The increased plasma homocysteine level significantly increased collagen deposition in the adventitia. There was a negative correlation (r = -0.698; P < 0.01) between the luminal area and the collagen content in the adventitia on day 28 following balloon injury. In cultured adventitial fibroblasts isolated from rat aorta, 100 micromol/L L-homocysteine (L-Hcy) significantly down-regulated matrix metalloproteinase-2 activity by 43% as determined by in vitro gelatin zymography (P < 0.05) and up-regulated the expression of collagen type I by 187% (P < 0.05) assessed by Western blotting. CONCLUSIONS: Hyperhomocysteinemia exacerbated vascular constrictive remodeling by accelerated neointima formation and collagen accumulation in the adventitia. Increased collagen deposition may be the underlying mechanism.
BACKGROUND: While hyperhomocysteinemia is associated with an increased risk of cardiovascular diseases, the effect of hyperhomocysteinemia on the vascular adventitia and vessel remodeling has not been clearly demonstrated. We investigated the effect of the hyperhomocysteinemia on adventitial hyperplasia and vascular remodeling following balloon injury in rats and the underlying mechanisms. METHODS:Rats were fed with diet containing methionine for 4 weeks to increase plasma homocysteine before balloon injury. Vascular geometrical changes were assessed at different time points following balloon injury. The collagen deposition was determined by picrosirius red staining and immunohistochemical staining. RESULTS: When compared with normal diet group, moderate hyperhomocysteinemia in methionine diet group significantly exacerbated adventitial hyperplasia at day 7 and collagen deposition mainly in the adventitia at day 28 following balloon injury. The increased plasma homocysteine level significantly increased collagen deposition in the adventitia. There was a negative correlation (r = -0.698; P < 0.01) between the luminal area and the collagen content in the adventitia on day 28 following balloon injury. In cultured adventitial fibroblasts isolated from rat aorta, 100 micromol/L L-homocysteine (L-Hcy) significantly down-regulated matrix metalloproteinase-2 activity by 43% as determined by in vitro gelatin zymography (P < 0.05) and up-regulated the expression of collagen type I by 187% (P < 0.05) assessed by Western blotting. CONCLUSIONS:Hyperhomocysteinemia exacerbated vascular constrictive remodeling by accelerated neointima formation and collagen accumulation in the adventitia. Increased collagen deposition may be the underlying mechanism.