Pathological ventricular remodeling: mechanisms: part 1 of 2

Abstract

Despite declines in heart failure morbidity and mortality with current therapies, rehospitalization rates remain distressingly high, substantially affecting individuals, society, and the economy. As a result, the need for new therapeutic advances and novel medical devices is urgent. Disease-related left ventricular remodeling is a complex process involving cardiac myocyte growth and death, vascular rarefaction, fibrosis, inflammation, and electrophysiological remodeling. Because these events are highly interrelated, targeting a single molecule or process may not be sufficient. Here, we review molecular and cellular mechanisms governing pathological ventricular remodeling.

Keywords: cardiac electrophysiology; fibrosis; inflammation; stem cells; ventricular remodeling.

Figure

Mechanisms of pathological ventricular remodeling. In response to pathophysiological stimuli, such as ischemia/reperfusion or excessive mechanical load, multiple molecular and cellular processes contribute to ventricular remodeling. These include cardiomyocyte loss through cell death pathways, such as necrosis, apoptosis, or possibly excessive autophagy. Cardiomyocytes become hypertrophic in response to both mechanical and neurohumoral triggers. Accumulation of excess extracellular matrix leads to fibrosis. Metabolic derangements, insulin resistance, and lipotoxicity can occur. Finally, structural changes and alterations in ion transporting processes culminate in a pro-arrhythmic phenotype.