The Effects of Progranulin in a Rat Model of Acute Myocardial Ischemia/Reperfusion are Mediated by Activation of the P13K/Akt Signaling Pathway.
Adipokines
/ pharmacology
Animals
Apoptosis
/ drug effects
Atherosclerosis
/ drug therapy
Chromones
/ pharmacology
Disease Models, Animal
Male
Morpholines
/ pharmacology
Myocardial Ischemia
/ physiopathology
Myocardial Reperfusion Injury
/ drug therapy
Myocardium
/ pathology
Myocytes, Cardiac
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Progranulins
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats
Rats, Wistar
Reperfusion Injury
/ drug therapy
Signal Transduction
/ drug effects
Journal
Medical science monitor basic research
ISSN: 2325-4416
Titre abrégé: Med Sci Monit Basic Res
Pays: United States
ID NLM: 101597444
Informations de publication
Date de publication:
07 Nov 2019
07 Nov 2019
Historique:
entrez:
8
11
2019
pubmed:
7
11
2019
medline:
31
3
2020
Statut:
epublish
Résumé
BACKGROUND Progranulin is an adipokine, encoded by the progranulin (GRN) gene. Progranulin is expressed in atherosclerosis, but its effects in cardiac ischemia and reperfusion injury are unknown. Therefore, this study aimed to investigate the effects of progranulin in a rat model of acute myocardial ischemia/reperfusion (MI/R) injury in vivo. MATERIAL AND METHODS The model of acute MI/R injury was established in male Wistar rats by ligation of the left anterior descending (LAD) coronary artery for 30 minutes and reperfusion for 60 minutes. Before modeling, one group was treated with progranulin (0.03 µg/kg), and one group was treated with the P13K/Akt inhibitor, LY294002 (3 mg/kg). Left ventricular function (LV) was monitored, including the LV systolic pressure (LVSP), LV end-diastolic pressure (LVEDP), and changes in LV pressure. At the end of the study, blood and myocardial tissue were examined. Cardiac biochemical markers, histopathology, gene expression, and apoptosis were analyzed. RESULTS Progranulin improved cardiac function following acute MI/R injury and significantly improved recovery of cardiac contractility and LVSP. Progranulin significantly reduced myocyte apoptosis, inflammation, and tissue edema, and was highly expressed in cardiac tissue following MI/R injury. The cardioprotective effect of progranulin was reduced by blocking the P13K/Akt signaling pathway. CONCLUSIONS In the rat model of acute MI/R injury, progranulin had a protective effect on cardiac function and morphology, associated with activation of the P13K/Akt signaling pathway. The mechanisms of the anti-apoptotic, anti-inflammatory, and inotropic effects of progranulin in the setting of acute MI/R injury require further in vivo studies.
Identifiants
pubmed: 31695019
pii: 916258
doi: 10.12659/MSMBR.916258
pmc: PMC6859783
doi:
Substances chimiques
Adipokines
0
Chromones
0
Morpholines
0
Progranulins
0
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
31M2U1DVID
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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