Glucagon-Like Peptide-1 Analog Liraglutide Attenuates Pressure-Overload Induced Cardiac Hypertrophy and Apoptosis throug
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ORIGINAL ARTICLE
Glucagon-Like Peptide-1 Analog Liraglutide Attenuates Pressure-Overload Induced Cardiac Hypertrophy and Apoptosis through Activating ATP Sensitive Potassium Channels Xiao-Jie Bai 1 & Jun-Tao Hao 2 & Rong-Hua Zheng 1 & Cai-Ping Yan 3 & Jin Wang 1 & Cai-Hong Yang 4 & Wei-Fang Zhang 5 & Zhi-Qing Zhao 6 Accepted: 22 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 μm2, p < 0.05) and apoptotic cells (17.5 ± 8.2 vs. 44.7 ± 7.9%, p < 0.05) were reduced. Expression of antiapoptotic 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 enddiastolic 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 channelmediated signaling pathway. These data suggest that liraglutide might be considered as an adjuvant therapy to treat patients with heart failure. Keywords Abdominal aortic constriction . Cardiac hypertrophy . Cardiac function . Glibenclamide . KATP channel . Liraglutide
* Xiao-Jie Bai [email protected] 1
2
Key Laboratory of Cellular Physiology, Ministry of Education, and the Departmen
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