Dr. Max-Paul Winter
MedUni Wien RESEARCHER OF THE MONTH March 2021
Interruption of vascular endothelial growth factor receptor 2 signaling induces a proliferative pulmonary vasculopathy and pulmonary hypertension
Pulmonary arterial hypertension (PAH) is a progressive, fatal disease that culminates in right heart failure and death within 2.8 years when left untreated. A proliferative vasculopathy with monoclonal growth of endothelial cells and total vessel occlusion represents the main pathologic finding associated with the disease. In the present study disruption of VEGF signaling due to direct ablative gene manipulation of Kdr in endothelial cells lead to a pulmonary hypertensive arteriopathy in rodents mimicking human PAH. Furthermore, the same vasculopathy could be observed in patients receiving anti-VEGF therapy. In both the experimental rodent model and in humans receiving anti-angiogenic therapy we found significantly elevated VEGFa serum levels. Overall, the present study could underline the critical role of the VEGF pathway in the pathogenesis of pulmonary hypertension.
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