1. Under biomechanical overload, cardiac fibroblasts and myocytes respond to an altered environment via multiple mechanisms including integrin-extracellular matrix interactions and renin-angiotensin-aldosterone axis activation. Cardiac fibroblasts increase synthesis of matrix proteins and secrete a variety of paracrine factors that can stimulate myocyte hypertrophy. Cardiac myocytes similarly respond by secreting a conglomerate of factors. Hormones such as TGFβ1, FGF2, and the IL-6 family members LIF and CT-1 have all been implicated in this bidirectional fibroblast-myocyte hormonal crosstalk.
2.The IL33/ST2 system in the heart. The IL-33/ST2 system is a recently described cardiac fibroblast-myocyte signaling system. This signaling pathway serves an antihypertrophic and cardioprotective mechanism in the face of biomechanical overload. IL-33 is produced by mechanically loaded cardiac fibroblasts and is possibly inactivated by caspases. Extracellular IL-33 may bind to a soluble “decoy” form of its receptor, sST2, and be removed from the biologically available pool, or it may bind a transmembrane form, ST2L, on the surface of cardiac myocytes. In the face of prohypertrophic stimuli in vitro or pressure overload in vivo, IL-33 appears to confer antihypertrophic and antifibrotic properties to the myocardium.