Dapagliflozin: a sodium–glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling

Autor: Xiaoming Chen, Qinyun Ruan, Changsheng Xu, Hailin Zhang, Jinzhang Zeng, Dajun Chai, Heng Du, Hong Xie, Jie Liu, Jinxiu Lin, Ke Ma, Yuze Zhang, Yong Chu, Xiaoyan Lin
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Endocrinology
Diabetes and Metabolism
Smad Proteins
SMAD
030204 cardiovascular system & hematology
Ventricular Function
Left
Rats
Sprague-Dawley
chemistry.chemical_compound
Ventricular Dysfunction
Left
0302 clinical medicine
Glucosides
Fibrosis
Dapagliflozin
Cells
Cultured
Original Investigation
0303 health sciences
Ventricular Remodeling
Angiotensin II
Hypertrophy
Left Ventricular
SGLT2 Inhibitor
Antifibrotic Agents
Cardiology and Cardiovascular Medicine
Signal Transduction
medicine.medical_specialty
Cardiac fibrotic remodeling
Transforming Growth Factor beta1
03 medical and health sciences
Diabetes mellitus
Internal medicine
medicine
Diseases of the circulatory (Cardiovascular) system
Animals
Benzhydryl Compounds
Sodium-Glucose Transporter 2 Inhibitors
030304 developmental biology
Sodium–glucose cotransporter 2 inhibitors
business.industry
Myocardium
Fibroblasts
medicine.disease
Disease Models
Animal
Blood pressure
Endocrinology
chemistry
Heart failure
RC666-701
TGFβ1/Smad signaling
business
Zdroj: Cardiovascular Diabetology
Cardiovascular Diabetology, Vol 20, Iss 1, Pp 1-15 (2021)
ISSN: 1475-2840
Popis: Background Cardiac remodeling is one of the major risk factors for heart failure. In patients with type 2 diabetes, sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of the first hospitalization for heart failure, possibly through glucose-independent mechanisms in part, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing cardiac remodeling and potential mechanisms. Methods Sprague–Dawley (SD) rats, induced by chronic infusion of Angiotensin II (Ang II) at a dose of 520 ng/kg per minute for 4 weeks with ALZET® mini-osmotic pumps, were treated with either SGLT2 inhibitor dapagliflozin (DAPA) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with Ang II (1 μM) with or without the indicated concentration (0.5, 1, 10 μM) of DAPA. The protein levels of collagen and TGF-β1/Smad signaling were measured along with body weight, and blood biochemical indexes. Results DAPA pretreatment resulted in the amelioration of left ventricular dysfunction in Ang II-infused SD rats without affecting blood glucose and blood pressure. Myocardial hypertrophy, fibrosis and increased collagen synthesis caused by Ang II infusion were significantly inhibited by DAPA pretreatment. In vitro, DAPA inhibit the Ang II-induced collagen production of CFs. Immunoblot with heart tissue homogenates from chronic Ang II-infused rats revealed that DAPA inhibited the activation of TGF-β1/Smads signaling. Conclusion DAPA ameliorates Ang II-induced cardiac remodeling by regulating the TGF-β1/Smad signaling in a non-glucose-lowering dependent manner.
Databáze: OpenAIRE
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