Aberrant growth of blood vessels termed 'angiogenesis'contributes to the pathology of several human diseases ranging from macular degeneration, retinopathy to inflammation and cancer. Recently small RNAs encoded in the genome termed microRNAs have been implicated in the regulation of diverse physiological processes including angiogenesis. We recently profiled microRNAs during activation of endothelial cells and identified microRNA-132 as a critical regulator of p120RasGAP during pathological neovascularization. In this proposal, I will characterize the role of miR-132/p120RasGAP in cell survival during stress responses in the vasculature using in vitro and in vivo angiogenesis models during the mentored phase. Using these models, in the independent phase, I will analyze the contribution of a different microRNA that functions as a negative regulator of cell survival in vascular cells. These studies will elucidate how distinct microRNA programs govern the balance between the pro and anti-angiogenic states in the vasculature during development and disease.
While the role of specific microRNAs (miR) in promoting endothelial activation has been well characterized, it is not clear how miRs regulate endothelial survival and apoptosis. In this proposal, during my K99 phase, I will address the role of angiomiR miR-132 in regulating cell survival in the vasculature. In the independent phase, I will analyze the contribution of a pro-apoptotic miR, miR-34 in mediating cell death in the vasculature and its effects on the Notch signaling pathway.
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