Integrins and integrin-related proteins in cardiac fibrosis

J Mol Cell Cardiol. 2016 Apr:93:162-74. doi: 10.1016/j.yjmcc.2015.11.010. Epub 2015 Nov 10.

Abstract

Cardiac fibrosis is one of the major components of the healing mechanism following any injury of the heart and as such may contribute to both systolic and diastolic dysfunction in a range of pathophysiologic conditions. Canonically, it can occur as part of the remodeling process that occurs following myocardial infarction or that follows as a response to pressure overload. Integrins are cell surface receptors which act in both cellular adhesion and signaling. Most importantly, in the context of the continuously contracting myocardium, they are recognized as mechanotransducers. They have been implicated in the development of fibrosis in several organs, including the heart. This review will focus on the involvement of integrins and integrin-related proteins, in cardiac fibrosis, outlining the roles of these proteins in the fibrotic responses in specific cardiac pathologies, discuss some of the common end effectors (angiotensin II, transforming growth factor beta 1 and mechanical stress) through which integrins function and finally discuss how manipulation of this set of proteins may lead to new treatments which could prove useful to alter the deleterious effects of cardiac fibrosis.

Keywords: Angiotensin; Fibrosis; Integrins; Mechanical stress; Myocardium; Transforming growth factor beta.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aging
  • Angiotensin II / metabolism
  • Animals
  • Blood Pressure
  • Carrier Proteins / metabolism*
  • Cytokines / metabolism
  • Diabetic Cardiomyopathies / etiology
  • Diabetic Cardiomyopathies / metabolism
  • Diabetic Cardiomyopathies / pathology
  • Epithelial-Mesenchymal Transition
  • Fibrosis
  • Humans
  • Integrins / metabolism*
  • Molecular Targeted Therapy
  • Myocardial Infarction / etiology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Protein Binding
  • Stress, Mechanical

Substances

  • Carrier Proteins
  • Cytokines
  • Integrins
  • Angiotensin II