TGF-beta1-Induced MAPK activation promotes collagen synthesis, nodule formation, redox stress and cellular senescence in porcine aortic valve interstitial cells.

Background and aim of the study: Aortic valve stenosis is a major cause of valve replacement, particularly in the elderly. TGF-β1 is upregulated in stenotic valves and induces calcification and collagen synthesis in cultured valve interstitial cells. It has been shown previously that TGF-β1 increases reactive oxygen species (ROS) in these cells in association with calcifying nodule formation, but the cellular signaling pathways responsible for these TGF-β1-induced effects are not well defined. Methods: Cultured porcine aortic valve interstitial cells were used to investigate the effects of inhibitors of TGF-β1 signaling pathways on 3 H-proline incorporation into the extracellular matrix, the peak number of calcifying nodules formed, redox stress as dichlorofluorescein diacetate (DCF-DA) fluorescence, and senescence-associated β-galactosidase staining. Results: Nodule formation and proline incorporation