Subcellular mechanisms underlying the convergence between redox and mechanic homeo...
Abstract
The study concerning on how cells adapt to distinct mechanical forces, translating physical stimulus in to chemical signals, is such a remarkable issue from mechanobiology, with direct implications on pathophysiology, particularly cardiovascular diseases. Growing evidences point out that redox pathways of cell signaling are fundamental mediators of mechanoadaptive responses. However, the mechanisms by which such physical stimuli promote controlled oxidant species generation and the local impact of these intermediates over effectors of cell mechanics control are still poorly known. The present project approaches such mechanisms through the hypothesis that the return to the tensional homeostasis after a mechanic challenge is mediated by fine tune regulation of redox processes. The main goal is to investigate the mechanisms regulating the convergence between redox and tensional homeostasis over the vascular structure and function - and specifics are: 1) to investigate in Vascular Smooth Muscle Cells (VSMC) how mechanic stimulation affects redox processes regulation which influences the mechanoresponse; 2) to analyze how the redox status modulation and oxidant species generation regulate the mechanic response in VSMC; and 3) to study in animal model the effects of physiologic and pathologic mechano stimulation in mechanisms regulating redox processes over mechanic adaptation in conductance vessel. The approaches include distinct mechanostressors in cells and tissues, coupled to real time analysis concerning molecular force sensors and modulation of subcellular oxidants and redox status. Overall, through these experiments will be possible to analyze compartmentalized redox events associated to cell and tissue mechanoadaptive responses. Such knowledge will contribute to get improves on mechanobiological/redox paradigm involving the homeostatic control and cardiovascular diseases development including vascular remodeling. (AU)