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Continuous Infusion of Angiotensin IV Protects against Acute Myocardial Infarction via the Inhibition of Inflammation and Autophagy.
- Source :
-
Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2021 Dec 14; Vol. 2021, pp. 2860488. Date of Electronic Publication: 2021 Dec 14 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- 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 7 <superscript>th</superscript> 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 30 <superscript>th</superscript> 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-) 1 β . 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.<br />Competing Interests: There were no competing financial interests in relation to the work.<br /> (Copyright © 2021 Wen-wu Bai et al.)
- Subjects :
- Angiotensin II administration & dosage
Angiotensin II pharmacology
Animals
Apoptosis
Cardiomyopathies etiology
Cardiomyopathies metabolism
Cardiomyopathies pathology
Cells, Cultured
Inflammation etiology
Inflammation metabolism
Inflammation pathology
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction etiology
Myocardial Infarction metabolism
Myocardial Infarction pathology
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Oxidative Stress
Rats
Angiotensin II analogs & derivatives
Autophagy
Cardiomyopathies prevention & control
Inflammation drug therapy
Myocardial Infarction prevention & control
Myocytes, Cardiac drug effects
Protective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0994
- Volume :
- 2021
- Database :
- MEDLINE
- Journal :
- Oxidative medicine and cellular longevity
- Publication Type :
- Academic Journal
- Accession number :
- 34950416
- Full Text :
- https://doi.org/10.1155/2021/2860488