Liu Cun-Fei, Zhang Jia, Shen Kai, Gao Ping-Jin, Wang Hai-Ya, Jin Xin, Meng Chao, Fang Ning-Yuan
Department of Geriatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China.
Division of Cardiology, Zhoushan People's Hospital, Zhoushan, Zhejiang 316000, P.R. China.
Mol Med Rep. 2015 Apr;11(4):2608-14. doi: 10.3892/mmr.2014.3069. Epub 2014 Dec 10.
Vascular adventitia and adventitia‑derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti‑oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII‑induced vascular remodeling in vivo. Adenoviruses co‑expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague‑Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen‑activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII‑induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII‑induced media hypertrophy compared with that of the control virus (P<0.05). In addition, catalase transfection significantly attenuated AngII‑induced ROS generation, macrophage infiltration, collagen deposition and adventitial α‑smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII‑induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII‑induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.
血管外膜及外膜衍生的活性氧(ROS)在血管损伤后参与血管重塑。先前一项针对外膜成纤维细胞的体外研究表明,过氧化氢酶作为最重要的抗氧化酶之一,会被血管紧张素II(AngII)下调。本研究的目的是探究过氧化氢酶的外膜基因转移是否会影响体内AngII诱导的血管重塑。将共表达过氧化氢酶和增强型绿色荧光蛋白(eGFP)或仅表达eGFP的腺病毒应用于Sprague-Dawley大鼠颈总动脉的外膜表面。然后皮下植入给予AngII(0.75mg/kg/天)的Alzet微型泵,持续14天。测量每组的收缩压和血管重塑的生物学参数。培养外膜成纤维细胞,并用蛋白质印迹分析测量p38丝裂原活化蛋白激酶(MAPK)的磷酸化。结果表明,过氧化氢酶的外膜基因转移对AngII诱导的收缩压升高没有影响。然而,与对照病毒相比,过氧化氢酶腺病毒转染显著抑制了AngII诱导的中膜肥厚(P<0.05)。此外,过氧化氢酶转染显著减弱了AngII诱导的ROS生成、巨噬细胞浸润、胶原蛋白沉积和外膜α平滑肌肌动蛋白表达。此外,过氧化氢酶转染显著抑制了AngII诱导的p38MAPK磷酸化增加。总之,本研究结果表明,过氧化氢酶的外膜基因转移通过抑制外膜p38MAPK磷酸化,显著减轻了大鼠体内AngII诱导的血管重塑。