Signaling via GPR30 protects the myocardium from ischemia/reperfusion injury

被引:89
作者
Weil, Brent R. [1 ]
Manukyan, Mariuxi C. [1 ]
Herrmann, Jeremy L. [1 ]
Wang, Yue [1 ]
Abarbanell, Aaron M. [1 ]
Poynter, Jeffrey A. [1 ]
Meldrum, Daniel R. [1 ,2 ,3 ,4 ]
机构
[1] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN USA
[2] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN USA
[3] Indiana Univ Sch Med, Ctr Immunobiol, Indianapolis, IN USA
[4] Methodist Hosp, Dept Clarian Cardiovasc Surg, Indianapolis, IN USA
关键词
ISCHEMIA-REPERFUSION INJURY; COUPLED RECEPTOR; SELECTIVE AGONIST; ESTROGEN; GENDER; ESTRADIOL; PATHWAY; TRAUMA; WOMEN; HEART;
D O I
10.1016/j.surg.2010.03.011
中图分类号
R61 [外科手术学];
学科分类号
100210 [外科学];
摘要
Background. Estrogen. may protect against the development of cardiovascular disease Recently, a receptor known as GPR30 that seems to mediate estrogen's nongenomic effects has been identified. We hypothesized that the activation of GPR30 protects cardiac function and decreases myocardial inflammation after global ischemia/reperfusion (I/R) Methods. Hearts from male Sprague-Dawley rats were perfused via Lnagendorff and treated with either (7) vehicle, (2) 10 min of the GPR30 against, G-1; or (3) 100 nm of G-1, they then were subjected to 25 minutes of ischemia and 40 minutes of reperfusion. Cardiac Junctional parameters were measured continuously. Ventricular tissue was analyzed for tumor necrosis factor (TNF)-alpha interleukin (IL)-1 beta and, IL-6. Results. At end-repo:fusion, the left ventricular developed pressure in the 100-nm G I group was improved compared with vehicle (26% +/- 12% equilibrium vs 54% +/- 9% equilibrium; P < 05) Similar findings were noted when comparing the 100-nm. G-1 group with the vehicle in terms of +dP/dt (53% +/- 12% equilibrium v.s 26% +/- 19%, respechvelv, P < .05) and -dP/dt (56% +/- 15% equilibrium vs 22% +/- 16% equilibrium, respectively, (P < 05). TNF-alpha, IL-1 beta, and IL-6 levels were lower m myocardium of the 100-nm G-1 group compared with the vehicle (P < 05) Conclusion. The GPR30 agonist, G-1, improves functional recovery and decreases myocardial inflammation after global I/R GPR30 may play an Important role in estrogen's ability to protect the heart against I/R injury. (Surgery 2010,148.436-43
引用
收藏
页码:436 / 443
页数:8
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