期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
卷 26, 期 2, 页码 179-188出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1074248420942007
关键词
liraglutide; hypertension; cardiac fibrosis; cardiac fibroblasts; reactive oxygen species
资金
- National Natural Science Foundation of China [81873459, U1804166]
- Supporting Plan for Scientific and Technological Innovative Talents in Universities of Henan Province [19HASTIT004]
The study found that liraglutide can reduce blood pressure and blood sugar in hypertensive mice, inhibit cardiac fibrosis, and decrease AT1R expression and ROS generation.
Background/Aims: Glucagon-like peptide-1 receptor agonist liraglutide has been reported to exert cardioprotective effects, but its effect on cardiac fibrosis remains controversial. The aim of this study was to investigate the effects of liraglutide on cardiac fibrosis and potential mechanisms. Methods: C57BL/6 mice (3-month old) were randomly divided into control, hypertension, and hypertension + liraglutide groups. The hypertensive state was created by infusion of Ang II (100 ng/kg center dot min) for 4 weeks through subcutaneously implanted osmotic pumps. The control mice were infused with saline. Mice were also given vehicle or liraglutide (400 mu g/kg center dot day). Blood pressure (BP), blood sugar, myocardial fibrosis, AT1R expression, and reactive oxygen species (ROS) levels were measured. To further elucidate the mechanisms of fibrosis, mouse cardiac fibroblasts were isolated and treated with liraglutide (300 nM/L) or losartan (10 mu M) for 3 hours, followed by Ang II (10(-7)M) for additional 12 hours. Reactive oxygen species production and expressions of collagen-1 and -3 were measured. Results: Liraglutide reduced BP and blood sugar but did not affect the body weight of the hypertensive mice. Liraglutide also inhibited collagen accumulation, AT1R expression, and ROS generation in the hearts of the hypertensive mice. In in vitro studies, pretreatment with liraglutide and losartan (as control) markedly inhibited Ang II-induced ROS production and collagen expression in the cultured cardiac fibroblasts. Conclusion: Liraglutide reduces myocardial fibrosis in the hypertensive mice, which appears to be dependent on at least in part inhibition of ROS production.
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