Molecular Pathways Underlying Cardiac Remodeling During Pathophysiological Stimulation

Abstract

Cardiac remodeling involves molecular, cellular, and interstitial changes that manifest clinically as changes in size, shape, and function of the heart after injury or stress stimulation.1 Although the term cardiac remodeling was initially coined to describe the prominent changes that occur after myocardial infarction,2,3 it is clear that similar processes transpire after other types of injury such as with pressure overload (aortic valve stenosis, hypertension), inflammatory disease (myocarditis), idiopathic dilated cardiomyopathy, and volume overload (valvular regurgitation). Although the causes of these diseases are different, they share molecular, biochemical, and cellular events to collectively change the shape of the myocardium. Cardiac hypertrophy is a common type of cardiac remodeling that occurs when the heart experiences elevated workload. The heart and individual myocytes enlarge as a means of reducing ventricular wall and septal stress when faced with increased workload or injury. Cardiac hypertrophy is classified as “physiological” when it occurs in healthy individuals after exercise or pregnancy and is not associated with cardiac damage. In contrast, hypertrophy that results from pressure or volume overload or after myocardial infarction is usually referred to as “pathological.” This name may be misleading, however, because pathological hypertrophy may also involve a compensatory and adaptive phase that tends to reduce wall stress and maintain output, although ultimately these positive aspects are lost and ventricular function declines, often leading to heart failure. In addition to ventricular remodeling, pathological cardiac hypertrophy involves cellular and molecular remodeling such as myocyte growth without significant proliferation, reexpression of fetal genes, alterations in the expression of proteins involved in excitation-contraction coupling, and changes in the energetic and metabolic state of the myocyte. These cellular and molecular changes within the myocyte are accompanied by changes in the extracellular matrix (ECM) and by myocyte death caused by necrosis or apoptosis. As …