Angiogenesis And Chronic Hypoxic Pulmonary Hypertension

Exposure to hypoxia leads to the development of pulmonary hypertension (PH) as a consequence of pulmonary smooth muscle hyperplasia. Hypoxia concomitantly stimulates lung expression of angiogenic factors. Increased expression of the angiogenic factor VEGF and its receptors has been found in the lungs of chronically hypoxic rats. In addition to VEGFA, VEGF C and D, other growth factors or cytokines including PDGF, acidic and basic FGF, transforming growth factor, angiogenin, and prostaglandin E2 have also been shown to increase during exposure to hypoxia, suggesting that activation of several lung angiogenic processes contribute to the lung adaptation to chronic hypoxia. Labeling studies also indicate that activation of lung angiogenic processes in response to hypoxia is associated with an increased number of peripheral pulmonary vessels. Pharmacological blockade of VEGF receptors or increased expression of antiangiogenic factors such as angiostatin, aggravate hypoxic pulmonary hypertension and structural vascular remodeling of pulmonary vessels. Concomitantly, these treatments decrease the number of peripheral pulmonary vessels. This suggests that activation of endogenous lung angiogenic processes during chronic hypoxia attenuates the severity of pulmonary hypertension by at least two mechanisms, protection against vascular remodeling and stimulation of peripheral vessel development.