title: Stretch-induced upregulation of connective tissue growth factor in rabbit cardiomyocytes.
abstract: Connective Tissue Growth Factor (CTGF, CCN2) is considered to play an important role in cardiac remodelling. We studied whether stretch is a primary stimulus to induce CTGF expression in vivo in rabbit heart, and in vitro in isolated cardiomyocytes and fibroblasts. Twenty weeks of combined volume and pressure overload resulted in eccentric left ventricular (LV) hypertrophy, with increased LV internal diameter (+36 %) and LV weight (+53 %). Myocardial CTGF mRNA and protein levels were substantially increased in the overloaded animals. In isolated adult rabbit cardiomyocytes, cyclic stretch strongly induced CTGF mRNA expression (2.9-fold at 48 h), whereas in cardiac fibroblasts CTGF-induction was transient and modest (1.4-fold after 4 h). Conditioned medium from stretched fibroblasts induced CTGF mRNA expression in non-stretched cardiomyocytes (2.3-fold at 48 h). Our findings indicate that stretch is an important primary trigger for CTGF-induction in the overloaded heart.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Blaauw
authors.forename: Ilka
authors.initials: I
authors.lastname: Lorenzen-Schmidt
authors.forename: Fawzi A
authors.initials: FA
authors.lastname: Babiker
authors.forename: Chantal
authors.initials: C
authors.lastname: Munts
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
authors.forename: Luc H
authors.initials: LH
authors.lastname: Snoeckx
authors.forename: Marc
authors.initials: M
authors.lastname: van Bilsen
authors.forename: Ger J
authors.initials: GJ
authors.lastname: van der Vusse
authors.forename: Frans A
authors.initials: FA
authors.lastname: van Nieuwenhoven
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D040542:Mechanotransduction, Cellular; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor