Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Life Sci. 2012 Feb 13;90(7-8):289-300. doi: 10.1016/j.lfs.2011.11.018. Epub 2011 Dec 19.
Recent findings have suggested that a therapeutic approach to amplify or stimulate the angiotensin-converting enzyme-2 [ACE-2]-angiotensin 1-7 [ANG 1-7] mas axis could provide protection against the development of cardiovascular diseases. We investigated the cardioprotective effects of telmisartan in rats with dilated cardiomyopathy [DCM] after experimental autoimmune myocarditis [EAM].
DCM was elicited in Lewis rats by immunization with cardiac myosin, and twenty-eight days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10mg/kg/day) or vehicle.
Telmisartan treatment effectively suppressed myocardial protein and mRNA expressions of inflammatory markers [CD68, iNOS, NF-kB, interleukin-1β, interferon-γ, monocyte chemotactic protein-1] in comparison to vehicle-treated rats. In contrast, myocardial protein levels of ACE-2 and ANG 1-7 mas receptor were upregulated in the telmisartan-treated group compared with vehicle-treated rats. Telmisartan treatment significantly reduced fibrosis and hypertrophy and their marker molecules [OPN, CTGF, TGF-β1 and collagens I and III and atrial natriuretic peptide and GATA-4, respectively] compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly lowered the protein expressions of NADPH oxidase subunits p47phox, p67phox, and superoxide production when compared with vehicle-treated rats. Telmisartan treatment significantly decreased the expression levels of mitogen-activated protein kinase (MAPK) signaling molecules than with those of vehicle-treated rats. Also, telmisartan treatment significantly improved LV systolic and diastolic function.
These results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling through the modulation of ACE-2/ANG 1-7/Mas receptor axis in rats with DCM after EAM.
最近的研究结果表明，一种通过血管紧张素转换酶-2（ACE-2）-血管紧张素 1-7（ANG 1-7）MAS 轴的放大或刺激的治疗方法可能对预防心血管疾病的发展提供保护。我们研究了替米沙坦在实验性自身免疫性心肌炎（EAM）后扩张型心肌病（DCM）大鼠中的心脏保护作用。
通过心肌肌球蛋白免疫诱导Lewis 大鼠产生 DCM，免疫后 28 天，存活的 Lewis 大鼠分为两组，分别给予替米沙坦（10mg/kg/天）或载体治疗。
与载体处理组相比，替米沙坦治疗有效抑制了心肌蛋白和炎性标志物[CD68、iNOS、NF-κB、白细胞介素-1β、干扰素-γ、单核细胞趋化蛋白-1]的 mRNA 表达。相比之下，与载体处理组相比，替米沙坦处理组心肌 ACE-2 和 ANG 1-7 MAS 受体蛋白水平上调。与载体处理组相比，替米沙坦治疗显著减少了纤维化和肥大及其标志物[OPN、CTGF、TGF-β1 以及胶原 I 和 III 和心钠肽和 GATA-4]。此外，与载体处理组相比，替米沙坦治疗显著降低了 NADPH 氧化酶亚基 p47phox、p67phox 和超氧化物的蛋白表达。替米沙坦治疗显著降低了丝裂原激活蛋白激酶（MAPK）信号分子的表达水平，与载体处理组相比。此外，替米沙坦治疗显著改善了 LV 收缩和舒张功能。
这些结果表明，替米沙坦治疗通过调节 EAM 后 DCM 大鼠 ACE-2/ANG 1-7/MAS 受体轴显著改善了 LV 功能并改善了心脏重构的进展。
