Integrins and integrin-related proteins in cardiac fibrosis

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.

Myocyte-fibroblast communication in cardiac fibrosis and arrhythmias: Mechanisms and model systems

“…Cardiomyocytes specifically interact with fibronectin on the cell surface via integrins which has been reviewed in this issue [73] and elsewhere [74, 75]. Though there are no studies that directly assess the functional role of fibronectin in the heart, findings from mouse models targeting members of the integrin complex suggest that cardiomyocyte disruption of fibronectin related interactions have detrimental effects on cardiac electrophysiology and function [74].…”

Notch: A multi-functional integrating system of microenvironmental signals

“…Fibrotic diseases are defined by excessive deposition of fibrotic ECM molecules, increased tissue stiffness, and can occur in most any tissue although fibrosis of the liver, lung, kidney, and heart represent the major impacts of fibrosis on human health. Given the increased ECM present in fibrotic tissues, it is not surprising that integrins figure predominantly in the pathology of fibrosis [97-99]. Adding to this, it has become apparent that Notch is also an important regulator of fibrosis in the lung, liver, kidney, and skin [100, 101].…”

The slow force response to stretch: Controversy and contradictions

“…39 The cytosolic β1 integrin subunit is known to be activated in response to stretch and its expression is enhanced by the activity of Ang II. 39 The cytosolic β1 integrin subunit is known to be activated in response to stretch and its expression is enhanced by the activity of Ang II.…”