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. 2010 Dec 21;122(25):2727-35.
doi: 10.1161/CIRCULATIONAHA.110.942268.

Molecular pathways underlying cardiac remodeling during pathophysiological stimulation

Izhak Kehat  1 , Jeffery D Molkentin
Affiliations

Molecular pathways underlying cardiac remodeling during pathophysiological stimulation

Izhak Kehat et al. Circulation. .
No abstract available

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Figures

Figure 1
Figure 1
Macroscopic and microscopic patterns of hypertrophy. (A) Macroscopically the heart can respond to stress by concentric hypertrophy with increased left ventricular wall thickness without an associated increase in chamber size, and eccentric hypertrophy in which the internal radius of the ventricle increases to a greater degree than wall thickness (top). (B) The macroscopic patterns of hypertrophy are usually associated with similar changes in cardiomyocytes. Concentric hypertrophy is characterized by assembly of contractile-protein units in parallel, resulting in a relative increase in the width of individual cardiac myocytes, while eccentric hypertrophy is characterized by assembly of contractile-protein units in series, with a relatively greater increase in the length of the myocyte (bottom). It should be noted that the normal heart and myocyte can develop both patterns of hypertrophy, and that concentric hypertrophy can switch to an eccentric pattern.
Figure 2
Figure 2
Ventricular remodeling patterns. Ventricular remodeling can be roughly classified based on geometric shape changes and the pathological or physiologic stimuli that evoke the changes. Exercise usually results in a physiological hypertrophy typified by the lack of fibrosis and the absence of fetal gene expression and chamber growth that is matched with wall and septal thickness growth. Pressure overload usually results in concentric hypertrophy, usually accompanied by fibrosis. Volume overload usually results in eccentric hypertrophy, and is associated with mild or no fibrosis. Except for physiologic hypertrophy, all other types of hypertrophic remodeling can progress to failure and dilation with dysfunctional myocytes.
Figure 3
Figure 3
Simplified diagram of key pathways involved in cardiac remodeling. Neurohumoral stresses are sensed by the membrane-bound receptors, while mechanical stresses are probably sensed by both membrane and sarcomeric stretch-activated mechanisms. These receptors signal through G proteins such as Gαq, Gαs, and Rho family members resulting in modulation phospholipase C, adenylyl and guanylyl cyclases to directly control downstream signaling effectors such as kinases and phosphatases. Calcineurin is a key transducing phosphatase, while kinases such as CaMKII and MAPK appear to have a role in cellular growth, and PKG I appears to have an anti-hypertrophic role. Adenylyl cyclase and PKA also regulate myocyte contractility along with PKCα. These signals culminate in altered transcription that includes the re-induction of the fetal gene program and new cellular growth.
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References

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