ABSTRACT
Adaptive and maladaptive growth of the heart involves significant increases in the size and sarcomeric content of the constituent cardiac myocytes, and these morphological responses reflect a genuine cellular hypertrophy (growth in the absence of division). Another facet of the hypertrophic response is that genes which are expressed during fetal development of the heart (e.g. atrial and B-type natriuretic peptides, fetally expressed isoforms of myofibrillar proteins) are upregulated in hypertrophy, and are often used as indices of the response. These changes are elicited by signals operating between and within cells. The principal hypothesis is that neurohumoral factors (e.g. endothelin-1 (ET1), α1-adrenergic agonists, angiotensin II (Ang II)) are released locally and act at cellsurface receptors on cardiac myocytes to initiate intracellular signaling events. These modulate cellular functions and lead to the changes in gene and protein expression which evoke the overall response. Much research has focused on identifying the intracellular signaling pathways which are modulated in hypertrophy, and on elucidating the specific roles of each.
