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

Tracey Gaspari; Melita Brdar; Huey Wen Lee; Iresha Spizzo; Yunshan Hu; Robert E Widdop; Richard W Simpson; Anthony E Dear

doi:10.1177/1479164115605000

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

Diab Vasc Dis Res. 2016 Jan;13(1):56-68. doi: 10.1177/1479164115605000. Epub 2015 Sep 25.

Authors

Tracey Gaspari¹, Melita Brdar¹, Huey Wen Lee¹, Iresha Spizzo¹, Yunshan Hu², Robert E Widdop¹, Richard W Simpson², Anthony E Dear³

Affiliations

¹ Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
² Department of Medicine, Monash University, Melbourne, VIC, Australia.
³ Department of Medicine, Monash University, Melbourne, VIC, Australia [email protected].

PMID: 26408644
DOI: 10.1177/1479164115605000

Abstract

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.

Keywords: Glucagon-like peptide-1 receptor agonist; anti-inflammatory; cardiac fibrosis; macrophage; oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

Ccl2 protein, mouse
Chemokine CCL2
I-kappa B Proteins
IL10 protein, mouse
Incretins
NF-kappa B p50 Subunit
Vasoconstrictor Agents
Vimentin
Angiotensin II
Interleukin-10
Nfkb1 protein, mouse
Liraglutide
Glucagon-Like Peptide-1 Receptor Agonists