Cardiac hypertrophy is the result of increased myocardial cell size responding to an increased workload and developmental signals. These extrinsic and intrinsic stimuli as key drivers of cardiac hypertrophy have spurred efforts to target their associated signaling pathways. The extracellular signal-regulated kinases 1/2 (ERK1/2), as an essential member of mitogen-activated protein kinases (MAPKs), has been widely recognized for promoting cardiac growth. Several modified transgenic mouse models have been generated through either affecting the upstream kinase to change ERK1/2 activity, manipulating the direct role of ERK1/2 in the heart, or targeting phosphatases or MAPK scaffold proteins to alter total ERK1/2 activity in response to an increased workload. Using these models, both regulation of the upstream events and modulation of each isoform and indirect effector could provide important insights into how ERK1/2 modulates cardiomyocyte biology. Furthermore, a plethora of compounds, inhibitors, and regulators have emerged in consideration of ERK, or its MAPK kinases, are possible therapeutic targets against cardiac hypertrophic diseases. Herein, is a review of the available evidence regarding the exact role of ERK1/2 in regulating cardiac hypertrophy and a discussion of pharmacological strategy for treatment of cardiac hypertrophy.
Keywords: ERK1/2; cardiac hypertrophy; cardiomyocyte; genetic approaches; pharmacological strategy.