title: Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype.
abstract: Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".
authors.affiliation: Dartmouth Medical School, Department of Surgery, Section of Vascular Surgery, Lebanon, NH 03756, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Carrão
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wagner
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Eva M
authors.initials: EM
authors.lastname: Rzucidlo
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.forename: John
authors.initials: J
authors.lastname: Hwa
authors.forename: Tamar R
authors.initials: TR
authors.lastname: Aprahamian
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Martin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists; D019899:Paracrine Communication; D021381:Protein Transport; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D055372:AMP-Activated Protein Kinases