![]() ![]() The alignment of these additional sarcomeres either in series or in parallel within the cell defines whether thicker or more elongated myocytes result. 9 This increase in size is generally due to an increase in the number of sarcomere units within each myocyte. The sine qua non of myocardial hypertrophy is an increase in cardiac myocyte size rather than an increase in cell number. Thus, in cardiac responses to a specific physiological or pathophysiological stimulus, intrinsic signaling pathways within the myocytes and crosstalk between myocytes and other cell populations within the heart play crucial and interdependent roles. In addition to directly affecting myocytes, the same factors can also affect the nonmyocyte cell populations in the heart. These factors can be either physical (myocardial wall tension, myocyte stretch, etc) or molecular/chemical (growth factors, cytokines, and other circulating or locally produced bioactive molecules). The differences between exercise- and pressure-induced hypertrophy exemplify the profound importance of extrinsic factors as determinants of myocardial morphology and function. In this review, we discuss new insights into molecular regulation of a myocardial hypertrophic response, focusing on the contribution of cell-cell crosstalk in the heart to this process. Thus, to fully understand the biology and pathobiology of the heart, the influences of this cellular crosstalk must be considered. 8 These distinct cell pools are not isolated from one another within the heart but instead interact physically and via a variety of soluble paracrine, autocrine, and endocrine factors (summarized in Figure 1). Recently, pluripotent cardiac “stem cells” have also been identified in the heart. The balance includes a broad array of additional cell types, including smooth muscle and endothelial cells of the coronary vasculature and the endocardium, fibroblasts and other connective tissue cells, mast cells, and immune system–related cells. The human heart contains an estimated 2 to 3 billion cardiac muscle cells, but they account for fewer than a third of the total number of cells in the heart. 6,7 This pathological progression demonstrates a mismatch between oxygen supply and demand, as the extent of cardiomyocyte hypertrophy is not matched by a corresponding increase in the arterial blood supply. 5 A prolonged increase in wall stress may result in progressive ventricular dilation and myocardial decompensation owing to ongoing myocyte death and fibrosis and, ultimately, heart failure and death. 3,4 Different forms of hemodynamic stress (hypertension, aortic stenosis, coarctation of the aorta, mitral regurgitation, and myocardial infarction, among others) increase intraventricular pressure or volume and lead to a hypertrophic response. 3 In the case of exercise-induced hypertrophy, the heart preserves the oxygen supply/demand, matching the proportional increases in cardiac myocyte size and the extent of coronary microvasculature. ![]() 2 This is facilitated by the capillary density of 3000 to 4000 compared with 500 to 2000 per 1 mm 2 in skeletal muscle and a tight regulation of the coronary blood flow. As an adaptation to this high oxygen demand, the heart maintains a high level of oxygen extraction of 70% to 80% compared with 30% to 40% in skeletal muscle. ![]() In humans, at a heart rate of 60 to 70 beats per minute, the oxygen consumption normalized per gram of myocardium is 20-fold higher than that of skeletal muscle at rest. 1 Thus, the heart still reigns supreme: “oundation of their life, the sovereign of everything within them, the sun of their microcosm, that on which all growth depends, from which all power proceeds” (William Harvey, 1628).Įffective myocardial function depends primarily on oxidative energy production. Nearly 2400 Americans die of cardiac causes each day, 1 death every 37 seconds. Customer Service and Ordering InformationĬardiovascular disease is a leading cause of death worldwide.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB). ![]()
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