Acute
myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide.
Angiotensin (Ang) IV possesses many
biological properties that are not yet completely understood. Therefore, we investigated the function and mechanism of Ang IV in AMI in in vivo and in vitro conditions. AMI was performed by
ligation of the left anterior descending coronary artery (LAD) in male C57 mice. Ang IV was continuously infused by a minipump 3 d before AMI for 33 d. The neonatal rat ventricular myocytes (NRVCs) were stimulated with Ang IV and cultured under hypoxic conditions. In vivo, Ang IV infusion significantly reduced the mortality after AMI. By the 7th day after AMI, compared with the AMI group, Ang IV reduced the inflammatory
cytokine expression. Moreover,
terminal deoxyribonucleotidyl transferase- (TDT-) mediated dUTP nick-end labeling (TUNEL) assay showed that Ang IV infusion reduced AMI-induced cardiomyocyte apoptosis. Compared with AMI, Ang IV reduced autophagosomes in cardiomyocytes and improved mitochondrial swelling and disarrangement, as assessed by transmission electron microscopy. By 30th day after AMI, Ang IV significantly reduced the ratio of heart weight to
body weight. Echocardiography showed that Ang IV improved impaired cardiac function.
Hematoxylin and
eosin (H&E) and Masson staining showed that Ang IV infusion reduced the
infarction size and myocardial
fibrosis. In vitro,
dihydroethidium (DHE) staining and comet assay showed that, compared with the
hypoxia group, Ang IV reduced oxidative stress and DNA damage.
Enzyme-linked
immunosorbent assay (ELISA) showed that Ang IV reduced
hypoxia-induced secretion of the
tumor necrosis factor- (TNF-) ɑ and
interleukin- (IL-) 1β. In addition, compared with the
hypoxia group, Ang IV reduced the transformation of light chain 3- (LC3-) I to LC3-II but increased p62 expression and decreased cardiomyocyte apoptosis. Overall, the present study showed that Ang IV reduced the inflammatory response, autophagy, and
fibrosis after AMI, leading to reduced
infarction size and improved cardiac function. Therefore, administration of Ang IV may be a feasible strategy for the treatment of AMI.