Recovery of endothelial integrity after vascular injury is vital for endothelial barrier function and vascular homeostasis. Endothelial dysfunction plays a critical role in the initiation and progression of vascular diseases such as atherosclerosis and acute lung injury. A part of the research in the lab is to elucidate the molecular mechanisms of endothelial repair, and endothelial progenitor cells-mediated endothelial regeneration and neovascularization using the unique mouse model with endothelial cell-restricted deletion of FoxM1 (J. Clin. Invest. 2006, 116: 2333).
Pulmonary hypertension is a progressive disease with high mortality. We have recently identified a novel molecular mechanism of pulmonary hypertension using genetic knockout mouse models and pharmacological approaches (J. Clin Invest. 2009, 119: 2009-2018). eNOS activation secondary to Caveolin-1 deficiency induces PH through nitration-mediated impairment of PKG activity. These main features of the molecular basis of PH identified in mouse models are recapitulated in lung tissues from patients with idiopathic pulmonary arterial hypertension. It is our goal to provide novel therapeutic approaches for the therapy of this devastating disease through inhibiting oxidative/nitrative stress-induced PKG nitration.