Mechanical stimuli frequently trigger signals leading to increase gene expression, protein synthesis, or mitogenesis. Cardiac fibroblasts respond to changes in ventricular hemodynamic loading by increasing matrix production in models of pressure-overload hypertrophy and myocardial infarction. Recent studies have identified some of the intracellular signaling pathways that mediate the biological effects observed upon mechanical stimulation in vitro. These include mitogenactivated protein kinases (MAPKs) and protein kinase C (PKC) family. MAPKs include extracellular signal-regulated kinase (ERK), C-Jun NH2-terminal kinase (JNK), and p38 MAPK. ERK pathway is frequently stimulated in response to mitogen.

Previous studies demonstrated that mechanical stretch stimulated MAPK activities in normal adult rat cardiac fibroblasts. On the other hand, mechanical stretch also increases transcription and production of the matrix proteins collagen (type I and HI) and fibronectin in cardiac fibroblasts. MAPKs are activated by mechanical stretch during cardiac myocytes hypertrophy through both PKCdependent and independent pathways.