血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)...血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)与正常对照大鼠(Wistar-Kyoto rats,WKY)的血管外膜成纤维细胞在体外培养条件下迁移能力的差别,并对其机制进行了探讨。采用大鼠胸主动脉的培养血管外膜成纤维细胞,用Transwell技术测定培养细胞的迁移能力。用实时定量PCR技术检测mRNA表达。结果表明,在血清和bFGF趋化作用下,SHR培养血管外膜成纤维细胞的迁移活性显著强于WKY(每个视野平均迁移细胞数目,血清:35.20±5.26 vs 22.2±3.27,P<0.05;bFGF:30.23±4.54vs 19.20±4.47,P<0.05)。进一步研究发现,SHR培养血管外膜成纤维细胞中的骨桥蛋白(osteopontin,OPN)mRNA水平显著高于WKY(1863.23±43.91 vs 326.24±68.29,P<0.01)。反义OPN(100 μmol/L)对血清诱导的SHR血管外膜成纤维细胞迁移有抑制作用(每个视野平均迁移细胞数目 38.60±5.98 vs 26.61±3.84,P<0.05)。而正义及错配义OPN组均无此效应。反义OPN对SHR细胞迁移的抑制作用呈浓度依赖性。上述结果证实SHR培养血管外膜成纤维细胞的迁移能力强于WKY。展开更多
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 demonstra...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 pmol/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.展开更多
基金This work was supported by the National Natural Science foundation of China(M3007030330270544).
文摘血管外膜成纤维细胞迁移参与形成新生内膜是一些血管疾病的共同发病过程。研究高血压动物模型的外膜成纤维细胞是否与对照组不同将有利于阐述高血压血管重塑的机制。本实验比较自发性高血压大鼠(spontaneously hy-pertensive rats,SHR)与正常对照大鼠(Wistar-Kyoto rats,WKY)的血管外膜成纤维细胞在体外培养条件下迁移能力的差别,并对其机制进行了探讨。采用大鼠胸主动脉的培养血管外膜成纤维细胞,用Transwell技术测定培养细胞的迁移能力。用实时定量PCR技术检测mRNA表达。结果表明,在血清和bFGF趋化作用下,SHR培养血管外膜成纤维细胞的迁移活性显著强于WKY(每个视野平均迁移细胞数目,血清:35.20±5.26 vs 22.2±3.27,P<0.05;bFGF:30.23±4.54vs 19.20±4.47,P<0.05)。进一步研究发现,SHR培养血管外膜成纤维细胞中的骨桥蛋白(osteopontin,OPN)mRNA水平显著高于WKY(1863.23±43.91 vs 326.24±68.29,P<0.01)。反义OPN(100 μmol/L)对血清诱导的SHR血管外膜成纤维细胞迁移有抑制作用(每个视野平均迁移细胞数目 38.60±5.98 vs 26.61±3.84,P<0.05)。而正义及错配义OPN组均无此效应。反义OPN对SHR细胞迁移的抑制作用呈浓度依赖性。上述结果证实SHR培养血管外膜成纤维细胞的迁移能力强于WKY。
文摘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 pmol/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.
