Fluvastatin protects myocardial cells in mice with acute myocardial infarction through inhibiting RhoA/ROCK pathway

Abstract

Protective effect of fluvastatin (Flu) on myocardial cells in mice with acute myocardial infarction (AMI) and the mechanism were explored. Forty C57B/L6 mice in similar physiological status were selected and randomly divided into sham operation (Sham) group (n=10), AMI group (n=10), Flu group (n=10) and Flu + Angiotensin II (Ang II) (Ang II) group (n=10). The pathological changes in heart tissues were detected via hematoxylin and eosin (H&E) staining, and apoptosis of myocardial cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined using relevant kits, and the expression levels of Ras homolog gene family (Rho)-associated coiled-coil protein kinase 1 (ROCK1), ROCK2, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and nuclear factor-κB (NF-κB) in the infarction region were determined using Western blotting. The infarction area in mice in Flu group was significantly smaller than that in AMI group. In AMI group, the level of MDA in the serum and infarction tissues was remarkably higher than that in Sham group (P<0.05), while that of SOD significantly declined (P<0.05). The level of MDA in Flu group was obviously lower than that in AMI group (P<0.05). The expression levels of Bax, NF-κB, ROCK1 and ROCK2 were obviously higher in AMI group than those in Sham group, while they were obviously lower in Flu group than those in AMI group (P<0.05). After the Rho member A (RhoA)/ROCK pathway agonist Ang II was added, the mitigation effect of Flu on myocardial apoptosis in the infarction region in AMI mice was evidently weakened. Flu mitigates AMI-induced myocardial apoptosis in mice, and the possible mechanism is that the inflammatory and oxidative stress responses activated and mediated by RhoA/ROCK are effectively inhibited.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

“…Previous studies have suggested that the oxidative stress levels are significantly elevated in AMI, which could cause myocardial cell dysfunction and damage [ 47 , 48 ]. In addition, excessive oxidative stress and an inflammatory response could promote the occurrence of heart failure in patients with AMI [ 49 ]. Based on the above evidence, we speculated that S100A12 may promote the inflammatory response, oxidative stress, and myocardial damage after AMI.…”

Dexmedetomidine prevents cardiomyocytes from hypoxia/reoxygenation injury via modulating tetmethylcytosine dioxygenase 1-mediated DNA demethylation of Sirtuin1

“…Afterward, the sections were added to 50 μL of DAB substrate solution and left to incubate for 10 minutes at room temperature. At last, the sections were sealed with glycerol, and a light microscope was employed for counting and photographing [ 39 ].…”

SERPINB1 overexpression protects myocardial damage induced by acute myocardial infarction through AMPK/mTOR pathway

“…Xu et al have suggested that leonurine inhibited myocardial apo ptosis and improved myocardial function in rat model by activating the PI3K/AKT/GSK3β pathway [ 33 ]. Yi et al has found that inhibition of RhoA/ROCK pathway significantly mitigated AMI-induced myocardial apoptosis in mice [ 34 ].The analogical results were obtained in our study. We found that AMI modeling inhibited the AMPK/mTOR pathway and induced myocardial apoptosis.…”