Biochemical Mechanisms of Cardiac Hypertrophy

Abstract

Rapid cardiac growth in adult rats and neonatal pigs involves more efficient use of existing components of the protein synthesis pathway and synthesis of new ribosomes and mRNA to increase the capacity for protein synthesis. Greater efficiency of synthesis can be induced by mechanical perturbations that stretch the ventricular wall, including increased cardiac work and increased ventricular pressure development in beating hearts, and increased aortic and intraventricular pressure in arrested-drained hearts. The biochemical signal linking stretch to more efficient protein synthesis has not been identified. Preferential synthesis of new ribosomes occurs in the first two hours of exposure of Langendorff preparations to high aortic pressure or within four hours after injection of thyroid hormone into normal rats. The rate of protein degradation is either accelerated or unchanged in hypertrophing hearts but is inhibited by induction of cardiac work or high aortic pressure in Langendorff preparations. Overall, increased capacity for, and efficiency of, protein synthesis are the major factors accounting for cardiac growth.

Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes

“…More importantly, hypertrophic agonist-induced expression of the embryonic gene ANF and enlargement of cardiomyocytes were abrogated by inhibition of NF-B activity but induced by overexpression of members of the NF-B family. These results demonstrate that the NF-B signaling pathway is required for hypertrophic growth of cardiomyocytes, a process that may lead to heart failure (27,29).…”

“…Another important feature of cardiomyocyte hypertrophy is the morphological changes of cardiomyocytes, such as enlargement in cell size (27). To determine whether inhibition of NF-B activation affects the hypertrophic morphology changes of primary cardiomyocytes, cells were transfected with the HA-I B␣ (32Ala͞36Ala) mutant or empty vector.…”

“…Cardiomyoyctes are terminally differentiated cells (27). In response to various extracellular stimuli, cardiomyoyctes grow in a hypertrophic manner, an event that is characterized by enlargement of individual cell size, an increase in the content of contractile proteins such as myosin heavy chain, and expression of embryonic genes such as atrial natriuretic factor (ANF) (27,28).…”

“…In response to various extracellular stimuli, cardiomyoyctes grow in a hypertrophic manner, an event that is characterized by enlargement of individual cell size, an increase in the content of contractile proteins such as myosin heavy chain, and expression of embryonic genes such as atrial natriuretic factor (ANF) (27,28). The collective result is cardiac hypertrophy, which is an adaptive and compensatory response in nature (28).…”

“…The collective result is cardiac hypertrophy, which is an adaptive and compensatory response in nature (28). However, sustained cardiac hypertrophy can set overt heart failure in motion (27).…”