title: Molecular and cellular mechanisms of glucagon-like peptide-1 receptor agonist-mediated attenuation of cardiac fibrosis.
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.
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
authors.forename: Tracey
authors.initials: T
authors.lastname: Gaspari
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
authors.forename: Melita
authors.initials: M
authors.lastname: Brdar
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
authors.forename: Huey Wen
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
authors.forename: Iresha
authors.initials: I
authors.lastname: Spizzo
authors.affiliation: Department of Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Widdop
authors.affiliation: Department of Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Simpson
authors.affiliation: Department of Medicine, Monash University, Melbourne, VIC, Australia Anthony.dear@monash.edu.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Dear
mesh_terms: D000375:Aging / Q000187:drug effects*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018932:Chemokine CCL2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology*; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D020672:I-kappa B Proteins / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D054795:Incretins / Q000494:pharmacology*; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics; D000069450:Liraglutide / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D052002:NF-kappa B p50 Subunit / Q000187:drug effects / Q000235:genetics; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; C556062:IL10 protein, mouse; D054795:Incretins; D052002:NF-kappa B p50 Subunit; D014662:Vasoconstrictor Agents; D014746:Vimentin; D000804:Angiotensin II; D016753:Interleukin-10; C073701:Nfkb1 protein, mouse; D000069450:Liraglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Glucagon-like peptide-1 receptor agonist; anti-inflammatory; cardiac fibrosis; macrophage; oxidative stress