The sodium–glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats

Autor: Yi Lin Shiou, Hsiang Chun Lee, Wun Jyun Jhuang, Yun Fang Chen, Chia Yuan Chang, Wei-Yu Chen, An-Sheng Lee, Shih Jie Jhuo, Zen Kong Dai, Po Len Liu
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
lcsh:Diseases of the circulatory (Cardiovascular) system
Cardiac fibrosis
Endocrinology
Diabetes and Metabolism
Empagliflozin
Hemodynamics
030204 cardiovascular system & hematology
PPARα
Rats
Inbred WKY
Ventricular Function
Left
0302 clinical medicine
Glucosides
Rats
Inbred SHR
Natriuretic Peptide
Brain
Original Investigation
medicine.diagnostic_test
Ventricular Remodeling
Fatty Acids
SGLT2 inhibitor
Hypertension
Cardiology
cardiovascular system
Atrial Function
Left
Sample collection
SGLT2 Inhibitor
Cardiology and Cardiovascular Medicine
Atrial Natriuretic Factor
medicine.medical_specialty
030209 endocrinology & metabolism
Heart failure
Diet
High-Fat
03 medical and health sciences
High-fat
Internal medicine
medicine
Animals
cardiovascular diseases
Benzhydryl Compounds
Ventricular remodeling
Sodium-Glucose Transporter 2 Inhibitors
ACADM
business.industry
Tumor Necrosis Factor-alpha
Myocardium
Hypertensive
Recovery of Function
medicine.disease
Fibrosis
Disease Models
Animal
Gene Expression Regulation
lcsh:RC666-701
business
Electrocardiography
Zdroj: Cardiovascular Diabetology
Cardiovascular Diabetology, Vol 18, Iss 1, Pp 1-13 (2019)
ISSN: 1475-2840
Popis: Background Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. Methods and results The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. Conclusions Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.
Databáze: OpenAIRE
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