Oxidative Stress and Redox Signalling in Cardiac Remodelling

Abstract

Cardiac remodelling describes the chronic response to stresses such as myocardial infarction (MI) or chronic hypertension, which generally becomes maladaptive over time, leading to deleterious structural and functional alterations and manifesting clinically as chronic heart failure (CHF). Although the underlying mechanisms are multifactorial, a significant body of evidence points to important roles for oxidative stress and redox signalling. Oxidative stress, occurring when excess reactive oxygen species (ROS) cannot be adequately countered by antioxidant defences, triggers cell dysfunction, energetic deficit or cell death. However, ROS may also have more subtle effects in the process of remodelling through specific modulation of redox-sensitive signalling pathways that alter gene and protein expression and function. ROS are generated from many sources including mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases; the last of these appear to be especially important in redox signalling. This chapter discusses recent advances in delineating the contribution of ROS to some of the principal alterations underlying the remodelling process (i.e., cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, contractile dysfunction, and chamber dilatation), with a particular emphasis on the role of NADPH oxidase. A better understanding of redox signalling mechanisms may enable the development of new targeted strategies for the prevention and treatment of adverse cardiac remodelling.