title: Temporal changes in integrin-mediated cardiomyocyte adhesion secondary to chronic cardiac volume overload in rats.
abstract: Previous studies have established integrins as cell surface receptors that mediate cardiomyocyte-extracellular matrix (ECM) attachments. This study sought to determine the contributions of the myocardial β1- and β3-integrin subunits to ventricular dilatation and coronary flow regulation using a blood-perfused isolated heart preparation. Furthermore, cardiomyocyte adhesion to collagen types I and IV, fibronectin, and laminin with and without a β1-integrin subunit neutralizing antibody was assessed during the course of remodeling secondary to a sustained cardiac volume overload, including the onset of heart failure. Isolated cardiomyocytes were obtained during the initial, compensated, and decompensated phases of remodeling resulting from an aortocaval fistula created in 8-wk-old male Sprague-Dawley rats. Blocking the β1-integrin subunit in isolated normal hearts produced ventricular dilatation, whereas this was not the case when the β3-subunit was blocked. Substantial reductions in cardiomyocyte adhesion coincided with the previously documented development of ventricular dilatation and decreased contractility postfistula, with the β1-integrin contribution to adhesion ranging from 28% to 73% over the course of remodeling being essentially substrate independent. In contrast, both integrin subunits were found to be involved in regulating coronary vascular resistance. It is concluded that marked reductions in integrin-mediated cardiomyocyte adhesion to the ECM play a significant role in the progression of adverse myocardial remodeling that leads to heart failure. Furthermore, although both the β1- and β3-integrin subunits were involved in regulating coronary vascular resistance, only inhibition of β1-integrin-mediated adhesion resulted in ventricular dilatation of the normal heart.
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina.
authors.forename: James A
authors.initials: JA
authors.lastname: Stewart
authors.forename: Jason D
authors.initials: JD
authors.lastname: Gardner
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Brower
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Janicki
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002306:Cardiac Volume; D002448:Cell Adhesion; D003326:Coronary Circulation; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism*; D039661:Integrin beta3 / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D057134:Antibodies, Neutralizing; D019012:Integrin beta1; D039661:Integrin beta3
keywords: aortocaval fistula; collagen types I and IV; coronary flow; extracellular matrix; fibronectin; heart failure; laminin; ventricular remodeling; β1- and β3-integrin subunits