Valsartan preconditioning protects against myocardial ischemia-reperfusion injury through TLR4/NF-kappaB signaling pathway.
Toll-like receptor 4 (TLR4) activation has been implicated in the pathogenesis of myocardial ischemia/reperfusion (I/R) injury. The activated TLR4 is capable of activating a variety of proinflammatory mediators, such as tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6). Valsartan as a kind of Angiotensin II type 1 receptor blockers is gradually used for the treatment of ischemic heart disease depending on its anti-inflammation function. Therefore, we hypothesized that valsartan protects against myocardial I/R injury by suppressing TLR4 activation. We constructed the rat model of myocardial I/R injury. The rats were pretreated with valsartan for 2 weeks, and then subjected to 30 min ischemia and 2 h reperfusion. TLR4 and Nuclear factor kappa-B (NF-kappaB) levels were detected by quantitative real-time PCR and western blot. In order to evaluate myocardial damage, the myocardial infarct size, histopathologic changes, and the release of myocardial enzymes, proinflammation cytokines and Angiotensin II were analyzed by triphenyl tetrazolium chloride (TTC) staining, light microscopy, and enzyme-linked immunosorbent assay (ELISA), respectively. Valsartan preconditioning inhibited TLR4 and NF-kappaB expressions concomitant with an improvement in myocardial injury, such as smaller infarct size, fewer release of myocardial enzymes, and proinflammation mediators. These findings suggest that valsartan plays a pivotal role in the protective effects on myocardial I/R injury. This protection mechanism is possibly due to its anti-inflammation function via TLR4/NF-kappaB signaling pathway.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Jian
J
Yang
Hong
H
Jiang
Jun
J
Yang
Jia-Wang
JW
Ding
Li-Hua
LH
Chen
Song
S
Li
Xiao-Dong
XD
Zhang
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D018836:Inflammation Mediators; D019157:Ischemic Preconditioning, Myocardial; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D018836:Inflammation Mediators; D016328:NF-kappa B; C495345:TLR4 protein, human; D013777:Tetrazoles; D051197:Toll-Like Receptor 4; D000068756:Valsartan; D014633:Valine