Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis

Background: Glucagon-like peptide-1 receptor agonists may have a role in modulation of cardiac fibrosis. Our study aimed to determine the effect of the glucagon-like peptide-1 receptor agonist liraglutide in obesity, hypertension and age-induced murine models of cardiac fibrosis and identify associa...

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Published in:	Diabetes & vascular disease research 2016-01, Vol.13 (1), p.56-68
Main Authors:	Gaspari, Tracey, Brdar, Melita, Lee, Huey Wen, Spizzo, Iresha, Hu, Yunshan, Widdop, Robert E, Simpson, Richard W, Dear, Anthony E
Format:	Article
Language:	eng
Subjects:	Aging - drug effects Angiotensin II - pharmacology Animals Aorta - drug effects Blood Pressure - drug effects Body Weight - drug effects Chemokine CCL2 - drug effects Chemokine CCL2 - genetics Chemokine CCL2 - metabolism Diet, High-Fat Disease Models, Animal Endothelium, Vascular - drug effects Fibrosis Glucagon-Like Peptide-1 Receptor - agonists Heart - drug effects Heart Diseases - metabolism Heart Diseases - pathology Hypertension - chemically induced Hypertension - metabolism I-kappa B Proteins - drug effects I-kappa B Proteins - metabolism Immunohistochemistry Incretins - pharmacology Inflammation Interleukin-10 - genetics Liraglutide - pharmacology Macrophages - drug effects Male Mice Mice, Inbred C57BL Myocardium - metabolism Myocardium - pathology NF-kappa B p50 Subunit - drug effects NF-kappa B p50 Subunit - genetics Obesity - metabolism Oxidative Stress - drug effects Real-Time Polymerase Chain Reaction Vasoconstrictor Agents - pharmacology Vimentin - drug effects Vimentin - metabolism
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Summary:	Background: Glucagon-like peptide-1 receptor agonists may have a role in modulation of cardiac fibrosis. Our study aimed to determine the effect of the glucagon-like peptide-1 receptor agonist liraglutide in obesity, hypertension and age-induced murine models of cardiac fibrosis and identify associated molecular mechanisms. Methods: C57Bl/6J mice on a high-fat diet and C57Bl/6J mice on a normal chow diet treated with angiotensin II were used to induce obesity and hypertension-mediated cardiac fibrosis, respectively. C57Bl/6J mice 20 months old were used to study age-induced cardiac fibrosis. Liraglutide treatment of 30 µg/kg/day–300 µg/kg s.c. twice daily was administered for 4 weeks. Results: Liraglutide treatment attenuated obesity, hypertension and age-induced increases in interstitial cardiac fibrosis and expression of inflammatory and oxidative stress markers. Conclusions: These observations identify a potential role for liraglutide in the prevention of cardiac fibrosis and identify molecular mechanisms associated with these effects.
ISSN:	1479-1641 1752-8984