![]() Macroscopically the heart responds to injury and stress in various ways. As the heart transitions from compensated hypertrophy to dilated heart failure, these cellular and molecular changes intensify resulting in myocyte lengthening, ECM remodeling, chamber dilation, and impaired systolic and/or diastolic function. 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. In addition to ventricular remodeling, pathologic cardiac hypertrophy involves cellular and molecular remodeling such as myocyte growth without significant proliferation, re-expression of fetal genes, alterations in the expression of proteins involved in excitation–contraction (E-C) coupling, and changes in the energetic and metabolic state of the myocyte. This name may be misleading though, 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 contrast, hypertrophy that results from pressure or volume overload or after myocardial infarction is usually referred to as “pathological”. Cardiac hypertrophy is classified as “physiological” when it occurs in healthy individuals following exercise or pregnancy and is not associated with cardiac damage. The heart and individual myocytes enlarge as a means of reducing ventricular wall and septal stress when faced with increased workload or injury. Although the etiologies of these diseases are different, they share molecular, biochemical and cellular events to collectively change the shape of the myocardium.Ĭardiac hypertrophy is a common type of cardiac remodeling that occurs when the heart experiences elevated workload. Although the term “cardiac remodeling” was initially coined to describe the prominent changes that occur following myocardial infarction 2, 3, it is clear that similar processes transpire following other types of injury such as with pressure overload (aortic valve stenosis, hypertension), inflammatory disease (myocarditis), idiopathic dilated cardiomyopathy, and volume overload (valvular regurgitation). Here we will highlight emerging concepts in cellular and ventricular remodeling and the more recent molecular signaling pathways that mediate these processes leading to disease, thereby suggesting novel therapeutic targets.Ĭardiac 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. Over the past 2 decades the use of genetically engineered mouse models has suggested nodal molecular regulator factors that mediate ventricular remodeling and the transition to heart failure with sustained pathophysiologic stimulation. Intracellular signal transduction cascades then transmit these stimuli throughout the cytoplasm and nucleus to alter cardiac gene expression, metabolism, protein turnover, and contractile function during the remodeling process. These different stimuli involve extrinsic signals in the form of neuroendocrine agonists and growth factors that are transduced through membrane bound receptors on cardiac myocytes, as well as intrinsic stress sensing associated with mechanical stretch. The heart is a dynamic organ capable of cellular and ventricular chamber remodeling in response to pathologic and physiologic stimulation.
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