Cyclic AMP reverses the pro-fibrogenic phenotype of cardiac myofibroblasts (850.3)

Previous data have shown that increased cellular levels of cyclic AMP (cAMP) can prevent the transformation of cardiac fibroblast (CFs) into pro-fibrogenic myofibroblasts (MyoFbs), a transformation that precedes increased extracellular matrix deposition and cardiac fibrosis. We have now investigated two additional roles for cAMP: 1) contribution to the MyoFb phenotype and 2) reversal of the MyoFb phenotype. We found that MyoFbs have lower cAMP content than do CFs, and in addition, have decreased mRNA and protein expression of isoforms of adenylyl cyclase (AC), including AC5 and AC6, the two major AC isoforms, and increased expression of several phosphodiesterase isoforms. Incubation of primary isolates of adult rat CFs with a pro-fibrotic stimulus, TGFβ1 (10ng/mL, 48hr), prominently increases mRNA and protein expression of collagen Iα1, Iα2, III, α-smooth muscle actin, plasminogen activator inhibitor-1 and cellular contractile state. All these hallmarks of the fibrogenic state were reversed in MyoFbs incu...