Anti-salusin-beta antibody enhances angiogenesis after myocardial ischemia reperfusion injury

作者:Masumura Mayumi; Watanabe Ryo; Nagashima Ayako; Ogawa Masahito; Suzuki Jun ichi*; Shichiri Masayoshi; Komuro Issei; Isobe Mitsuaki
来源:Expert Opinion on Therapeutic Targets, 2013, 17(9): 1003-1009.
DOI:10.1517/14728222.2013.819852

摘要

Backgrounds: Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-beta stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-beta has potent hypotensive, bradycardic and proatherosclerotic effects. %26lt;br%26gt;Objectives: To investigate whether salusin-beta plays a role in myocardial remodeling after myocardial ischemia reperfusion (I/R) injury, rat I/R models were created by the left anterior descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of reperfusion (control, n = 6 each). %26lt;br%26gt;Results and Conclusion: Immunohistochemical double staining showed the enhanced expression of salusin-beta in the macrophages around myocardial ischemic area. Anti-salusin-beta treated groups were administered the neutralizing salusin-beta antibody (10 mu l/day, i.p.) once daily from day -1 to day 1 or from day -1 to day 7 (anti-salusin-beta, n = 6 each). The anti-salusin-beta therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion. The small vessels (%26lt; 40 mu m in diameter) of I/R hearts treated with anti-salusin-beta were more densely populated than those of control animals (108.5 +/- 19.7 vs 47.5 +/- 2.4, p %26lt; 0.05). Real-time PCR revealed that the anti-salusin-beta therapy-induced angiogenesis was not associated with enhanced vascular endothelial growth factor A expression. The authors, for the first time, have clarified that endogenous salusin-beta suppresses angiogenesis which is critical in the development of cardiac remodeling following I/R injury.

  • 出版日期2013-9