A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling

Figure 2

Cardiac hypertrophy (a) and cardiac fibrosis (b) signaling pathways. Several molecules participate in the modulation of genes involved in cardiac hypertrophy. The transcription factor NFAT, responsible for cardiac hypertrophy, is positively regulated through calmodulin/calcineurin. In contrast, GSK3β inhibits cytoplasm-nucleus translocation of NFAT. HDAC4/HDAC5 also represses transcriptional activity of hypertrophic signals. Angiotensin II is the main mediator of cardiac fibrosis; AT1 receptor and ROS lead to TGFβ activation. This latter, through a SMAD-dependent or -independent pathway, activates the fibrotic genetic program, which consists in fibroblast proliferation, leukocyte infiltration, matrix degradation, collagen deposition, and myofibroblastic transdifferentiation.

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