Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is strong evidence for the use of angiotensin converting enzyme inhibitors and beta-blockers to reduce morbidity and mortality in patients with myocardial infarction (MI), whereas the effect of angiotensin receptor blockers is less clear. We evaluated the effects of an angiotensin receptor blocker losartan and a beta-blocker metoprolol on left ventricular (LV) remodeling, c-kit+ cells, proliferation, fibrosis, apoptosis, and angiogenesis using a model of coronary ligation in rats. Metoprolol treatment for 2 weeks improved LV systolic function. In contrast, losartan triggered deleterious structural remodeling and functional deterioration of LV systolic function, ejection fraction being 41% and fractional shortening 47% lower in losartan group than in controls 2 weeks after MI. The number of c-kit+ cells as well as expression of Ki-67 was increased by metoprolol. Losartan-induced thinning of the anterior wall and ventricular dilation were associated with increased apoptosis and fibrosis, while losartan had no effect on the expression of c-kit or Ki-67. Metoprolol or losartan had no effect on microvessel density. These results demonstrate that beta-blocker treatment attenuated adverse remodeling via c-kit+ cells and proliferation, whereas angiotensin receptor blocker-induced worsening of LV systolic function was associated with increased apoptosis and fibrosis in the peri-infarct region.
 ...
PMID:Divergent effects of losartan and metoprolol on cardiac remodeling, c-kit+ cells, proliferation and apoptosis in the left ventricle after myocardial infarction. 2044 34

The present study aimed to test whether angiotensin receptor blockers (ARBs) are cardioprotective after myocardial infarction (MI) by preventing augmented local renin-angiotensin-system (RAS)-induced oxidative stress injury and senescence, preserving resident stem cells, and restoring the insulin-like growth factor (IGF-1)/IGF-1 receptor (IGF-R) pathway. Sprague-Dawley rats with ligated or unligated coronary arteries were treated with losartan (20 mg/kg/d) or vehicle for 3 or 9 weeks. Heart function and molecular and histological changes were assessed. It was found MI induced left ventricular dysfunction and remodeling, increased levels of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine and cell senescence marker p16ink4a, and downregulated the IGF-1/IGF-1R/Akt pathway after both 3 and 9 weeks post-MI. MI induced an increase in stem cells identified by immunostaining for c-kit and Wilms' tumor-1 predominantly after 3 weeks. Losartan significantly inhibited local cardiac RAS activation and improved left ventricular function and remodeling at both timepoints. Losartan also preserved c-kit- and Wilms' tumor-1-positive cells (particularly at 3 weeks), attenuated 8-hydroxy-2'-deoxyguanosine- and p16ink4a-positive cardiomyocytes, and restored the IGF-1/IGF-1R/Akt pathway at both 3 and 9 weeks. In conclusion, ARBs aided cardiac repair post-MI through short-term preservation of stem cells and persistent anti-oxidative stress and anti-senescence effects, partially by attenuating activation of cardiac RAS and restoring the local IGF-1/IGF-1R/Akt pathway.
 ...
PMID:Angiotensin II receptor blocker reverses heart failure by attenuating local oxidative stress and preserving resident stem cells in rats with myocardial infarction. 3021 Jun 78