Canagliflozin attenuates hypertension induced myocardial hypertrophy and fibrosis via RAS and TGF-β1/Smad pathway

Objective: To investigate the effects of cagliazin, a sodium-glucose cotransporter 2 inhibitor (SGLT-2I), on ventricular remodeling in spontaneously hypertensive rats (SHR) through renin angiotensin system (RAS) and transforming growth factor -β1(TGF-β1). Methods: The experiment was divided into 4 groups: normal blood pressure control group, SHR group, cagliet net low-dose group (30mg/kg), cagliet net high-dose group (60mg/kg), once a day for 8 weeks. Normal blood pressure rats (WKY) were used as the control group to measure blood pressure with tail sleeve sphygmomanometer (BP) and blood glucose level was measured with glucose meter Cardiac function was evaluated by echocardiography, cell area of left ventricle was evaluated by histomorphology, real-time quantitative polymerase chain reaction and protein imprinting hybridization were used to detect TGF-β1 Smad4 renin from type I collagen (Col1a) type Ⅲ collagen (Col3a) matrix metalloproteinase 2(MMP-2) Expression results of angiotensin Ⅱ1 type receptor 1(AGTR1) and Angiotensin Ⅱ2 type receptor 2 (AGTR2). Results:After 8 weeks of administration, the cardiac weight/body weight ratio (HW/BW) of left ventricular weight/heart weight ratio (LVW/HW) of kaglinet low-dose group and high-dose group was statistically significant compared with that of spontaneous hypertensive rats (P< Compared with SHRs, the expression of Col1a, Col3a, MMP2, TGF-β1, Smad4, Renin AGTR1 was significantly down-regulated and the expression of AGTR2 was up-regulated in cagliet net low-dose and high-dose groups Conclusions: Cagliazin can improve hypertension-induced cardiac remodeling by regulating RAS and TGF-β1/Smad signaling pathways. Conclusion: From the results, canaglifozin was found to ameliorate pressure overload-induced cardiac remodeling by regulating the RAS and TGF-β1/Smad signaling pathway.