title: The antidiabetic hormone glucagon-like peptide-1 induces formation of new elastic fibers in human cardiac fibroblasts after cross-activation of IGF-IR.
abstract: Glucagon-like peptide 1 (GLP-1) is a metabolic hormone involved in the stimulation of insulin biosynthesis and secretion. It has been recently reported that GLP-1 also exerts cardioprotective effects and facilitates functional recovery after myocardial infarction through GLP-1 receptor-mediated signaling in cardiomyocytes. GLP-1 treatment has been also demonstrated to produce sustained improvement in cardiac function in long-term studies, suggesting the involvement of mechanisms beyond the acute metabolic and cytoprotective effects. For example, the possible interaction of GLP-1 with the cardiac fibroblasts, which are responsible for the postinfarct remodeling and extracellular matrix production, has not been previously explored. Here, we report that cultures of human cardiac fibroblasts treated with GLP-1 peptides display a selective up-regulation in elastin gene expression and a consequent increase in elastic fibers production, in the absence of the classic GLP-1 receptor. Importantly, we provide experimental evidence that this GLP-1-induced elastogenesis is triggered through the cross-activation of the IGF-I receptor. Because GLP-1 does not stimulate deposition of collagen I, nor promote the proliferation or apoptosis of cultured cardiac fibroblasts, we speculate that its elastogenic effect may also contribute to the beneficial remodeling of the human heart after myocardial infarction.
authors.affiliation: Physiology and Experimental Medicine Program (N.Q., Y.W., A.W., S.M., M.V., A.H.), Heart Center, The Hospital for Sick Children, Ontario, Canada M5G 0A4; Institute of Medical Science (N.Q., A.H.), University of Toronto, Ontario, Canada M5S 1A8; Department of Laboratory Medicine and Pathobiology (M.V., M.H., A.H.), University of Toronto, Ontario, Canada M5S 1A8; Heart and Stroke Richard Lewar Center of Excellence in Cardiovascular Research (M.H., A.H.), University of Toronto, Ontario, Canada M5S 1A8; and Toronto General Research Institute (M.H.), Toronto, Ontario, Canada M5G 2M9.
authors.forename: Nour
authors.initials: N
authors.lastname: Qa'aty
authors.forename: Yanting
authors.initials: Y
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Mao
authors.forename: Matthew
authors.initials: M
authors.lastname: Vincent
authors.forename: Mansoor
authors.initials: M
authors.lastname: Husain
authors.forename: Aleksander
authors.initials: A
authors.lastname: Hinek
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D049109:Cell Proliferation; D004547:Elastic Tissue / Q000254:growth & development*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000166:cytology*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D052216:Glucagon-Like Peptide 1; D017526:Receptor, IGF Type 1