Pretreatment with KGA-2727, a selective SGLT1 inhibitor, is protective against myocardial infarction-induced ventricular remodeling and heart failure in mice
| Autor: | Masamichi Hirose, Maki Saito, Naoko Matsushita, Miho Ibi, Eiichi Taira, Yoshihiro Morino, Yohei Sawa, Nanae Ishida |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Myocardial Infarction Cardiomyopathy Anterior Descending Coronary Artery Mice 03 medical and health sciences Sodium-Glucose Transporter 1 0302 clinical medicine Glucosides Internal medicine medicine Animals RNA Messenger Myocardial infarction cardiovascular diseases Ventricular remodeling Heart Failure Pharmacology Ischemic cardiomyopathy Ventricular Remodeling business.industry lcsh:RM1-950 medicine.disease Fibrosis Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Gene Expression Regulation Ventricle Heart failure Cardiology cardiovascular system Pyrazoles Molecular Medicine Myocardial fibrosis business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Pharmacological Sciences, Vol 142, Iss 1, Pp 16-25 (2020) |
| ISSN: | 1347-8613 |
| Popis: | Recent studies demonstrated that sodium-glucose co-transporter 1 (SGLT1) is associated with human ischemic cardiomyopathy. However, whether SGLT1 blockade is effective against ischemic cardiomyopathy is still uncertain. We examined the effects of KGA-2727, a selective SGLT1 inhibitor, on myocardial infarction (MI)-induced ischemic cardiomyopathy.To create MI, left anterior descending coronary artery (LAD) ligation with or without KGA-2727 administration was performed in C57BL/6J mice. Four weeks after the operation, all mice were investigated.Left ventricular fractional shortening (LVFS) was reduced and KGA-2727 significantly improved it in LAD-ligated MI mice. The cardiomyocyte diameter, and ANP, BNP, β-MHC, and IL-18 gene expressions significantly increased in LAD-ligated mouse left ventricles compared with those of sham-operated mouse left ventricles, and KGA-2727 inhibited increases in them. Myocardial fibrosis and upregulation of CTGF and MMP-3 gene expressions in the left ventricle were increased in LAD-ligated mice compared with sham-operated mice, and KGA-2727 decreased them in the LAD-ligated left ventricles. SGLT1 protein expression level was significantly higher in LAD-ligated compared with sham-operated mouse ventricles regardless of KGA-2727 treatment.These results suggest that KGA-2727 pretreatment protects against MI-induced left ventricular remodeling through SGLT1 blockade and that it may become a new pharmacological therapy for ischemia-induced cardiomyopathy. Keywords: Sodium/glucose co-transporter 1, Myocardial infarction, Cardiomyocyte hypertrophy, Myocardial fibrosis, Heart failure |
| Databáze: | OpenAIRE |
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