Glucagon-Like Peptide-1 Analog Liraglutide Attenuates Pressure-Overload Induced Cardiac Hypertrophy and Apoptosis through Activating ATP Sensitive Potassium Channels.

Autor: Bai XJ; Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China. baixiaojie_1973@163.com., Hao JT; Department of Thoracic surgery, Shanxi provincial people's hospital, Taiyuan, Shanxi, People's Republic of China., Zheng RH; Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China., Yan CP; Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China., Wang J; Key Laboratory of Cellular Physiology, Ministry of Education, and the Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China., Yang CH; Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China., Zhang WF; Functional Laboratory center, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China., Zhao ZQ; Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA, USA.
Jazyk: angličtina
Zdroj: Cardiovascular drugs and therapy [Cardiovasc Drugs Ther] 2021 Feb; Vol. 35 (1), pp. 87-101. Date of Electronic Publication: 2020 Oct 15.
DOI: 10.1007/s10557-020-07088-5
Abstrakt: Purpose: This study aimed to investigate whether inhibition of glucagon-like peptide-1 (GLP-1) on pressure overload induced cardiac hypertrophy and apoptosis is related to activation of ATP sensitive potassium (KATP) channels.
Methods: Male SD rats were randomly divided into five groups: sham, control (abdominal aortic constriction), GLP-1 analog liraglutide (0.3 mg/kg/twice day), KATP channel blocker glibenclamide (5 mg/kg/day), and liraglutide plus glibenclamide.
Results: Relative to the control on week 16, liraglutide upregulated protein and mRNA levels of KATP channel subunits Kir6.2/SUR2 and their expression in the myocardium, vascular smooth muscle, aortic endothelium, and cardiac microvasculature. Consistent with a reduction in aortic wall thickness (61.4 ± 7.6 vs. 75.0 ± 7.6 μm, p < 0.05), liraglutide enhanced maximal aortic endothelium-dependent relaxation in response to acetylcholine (71.9 ± 8.7 vs. 38.6 ± 4.8%, p < 0.05). Along with a reduction in heart to body weight ratio (2.6 ± 0.1 vs. 3.4 ± 0.4, mg/g, p < 0.05) by liraglutide, hypertrophied cardiomyocytes (371.0 ± 34.4 vs. 933.6 ± 156.6 μm 2 , p < 0.05) and apoptotic cells (17.5 ± 8.2 vs. 44.7 ± 7.9%, p < 0.05) were reduced. Expression of anti-apoptotic protein BCL-2 and contents of myocardial ATP were augmented, and expression of cleaved-caspase 3 and levels of serum Tn-I/-T were reduced. Echocardiography and hemodynamic measurement showed that cardiac systolic function was enhanced as evidenced by increased ejection fraction (88.4 ± 4.8 vs. 73.8 ± 5.1%, p < 0.05) and left ventricular systolic pressure (105.2 ± 10.8 vs. 82.7 ± 7.9 mmHg, p < 0.05), and diastolic function was preserved as shown by a reduction of ventricular end-diastolic pressure (-3.1 ± 2.9 vs. 6.7 ± 2.8 mmHg, p < 0.05). Furthermore, left ventricular internal diameter at end-diastole (5.8 ± 0.5 vs. 7.7 ± 0.6 mm, p < 0.05) and left ventricular internal diameter at end-systole (3.0 ± 0.6 vs. 4.7 ± 0.4 mm, p < 0.05) were improved. Dietary administration of glibenclamide alone did not alter all the parameters measured but significantly blocked liraglutide-exerted cardioprotection.
Conclusion: Liraglutide ameliorates cardiac hypertrophy and apoptosis, potentially via activating KATP channel-mediated signaling pathway. These data suggest that liraglutide might be considered as an adjuvant therapy to treat patients with heart failure.
Databáze: MEDLINE
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