Fei Xue1, Jianmin Yang1, Jing Cheng1, Wenhai Sui1, Cheng Cheng1, Hongxuan Li1, Meng Zhang1, Jie Zhang1, Xingli Xu1, Jing Ma1, Lin Lu1, Jinfeng Xu2, Meng Zhang1, Yun Zhang1, Cheng Zhang1. 1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China. 2. Department of Ultrasound, Shenzhen People's Hospital, Shenzhen, China.
Abstract
BACKGROUND AND PURPOSE: To test the hypothesis that angiotensin-(1-7) [Ang-(1-7)] may attenuate abdominal aortic aneurysm (AAA) via inhibiting vascular inflammation, extracellular matrix degradation, and smooth muscle cell (SMC) apoptosis, an animal model of AAA was established by angiotensin II (Ang II) infusion to apolipoprotein E-knockout (ApoE-/- ) mice. EXPERIMENTAL APPROACH: All mice and cultured SMCs or macrophages were divided into control, Ang II-treated, Ang II + Ang-(1-7)-treated, Ang II + Ang-(1-7) + A779-treated and Ang II + Ang-(1-7) + PD123319-treated groups respectively. In vivo, aortic mechanics and serum lipids were assessed. Ex vivo, AAA were examined by histology, immunohistochemistry and zymography. Cultured cells were analysed by RT-PCR, western blots and TUNEL assays. KEY RESULTS: In vivo, Ang-(1-7) reduced the incidence and severity of AAA induced by Ang II infusion, by inhibiting macrophage infiltration, attenuating expression of IL-6, TNF-α, CCL2 and MMP2, and decreasing SMC apoptosis in abdominal aortic tissues. Addition of A779 or PD123319 reversed Ang-(1-7)-mediated beneficial effects on AAA. In vitro, Ang-(1-7) decreased expression of mRNA for IL-6, TNF-α, and CCL2 induced by Ang II in macrophages. In addition, Ang-(1-7) suppressed apoptosis and MMP2 expression and activity in Ang II-treated SMCs. These effects were accompanied by inhibition of the ERK1/2 signalling pathways via Ang-(1-7) stimulation of Mas and AT2 receptors. CONCLUSION AND IMPLICATIONS: Ang-(1-7) treatment attenuated Ang II-induced AAA via inhibiting vascular inflammation, extracellular matrix degradation, and SMC apoptosis. Ang-(1-7) may provide a novel and promising approach to the prevention and treatment of AAA.
BACKGROUND AND PURPOSE: To test the hypothesis that angiotensin-(1-7) [Ang-(1-7)] may attenuate abdominal aortic aneurysm (AAA) via inhibiting vascular inflammation, extracellular matrix degradation, and smooth muscle cell (SMC) apoptosis, an animal model of AAA was established by angiotensin II (Ang II) infusion to apolipoprotein E-knockout (ApoE-/- ) mice. EXPERIMENTAL APPROACH: All mice and cultured SMCs or macrophages were divided into control, Ang II-treated, Ang II + Ang-(1-7)-treated, Ang II + Ang-(1-7) + A779-treated and Ang II + Ang-(1-7) + PD123319-treated groups respectively. In vivo, aortic mechanics and serum lipids were assessed. Ex vivo, AAA were examined by histology, immunohistochemistry and zymography. Cultured cells were analysed by RT-PCR, western blots and TUNEL assays. KEY RESULTS: In vivo, Ang-(1-7) reduced the incidence and severity of AAA induced by Ang II infusion, by inhibiting macrophage infiltration, attenuating expression of IL-6, TNF-α, CCL2 and MMP2, and decreasing SMC apoptosis in abdominal aortic tissues. Addition of A779 or PD123319 reversed Ang-(1-7)-mediated beneficial effects on AAA. In vitro, Ang-(1-7) decreased expression of mRNA for IL-6, TNF-α, and CCL2 induced by Ang II in macrophages. In addition, Ang-(1-7) suppressed apoptosis and MMP2 expression and activity in Ang II-treated SMCs. These effects were accompanied by inhibition of the ERK1/2 signalling pathways via Ang-(1-7) stimulation of Mas and AT2 receptors. CONCLUSION AND IMPLICATIONS: Ang-(1-7) treatment attenuated Ang II-induced AAA via inhibiting vascular inflammation, extracellular matrix degradation, and SMC apoptosis. Ang-(1-7) may provide a novel and promising approach to the prevention and treatment of AAA.
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