Current review focusing on the enigmatic role of VEGF in the pathogenesis of pulmonary arterial hypertension from American Journal of Respiratory Cell and Molecular Biology published online last month.
Pulmonary arterial hypertension (PAH) is characterized by dysfunctional angiogenesis leading to lung vessel obliteration. PAH is widely considered a pro-angiogenic disease, however, the role of angiogenic factors such as the vascular endothelial factor (VEGF) and its receptors in the pathobiology of PAH remains incompletely understood. This review attempts to untangle some of the complex multilayered actions of VEGF, in order to provide a VEGF-centered perspective of PAH. Furthermore, we provide a cogent explanation for the paradox of VEGF receptor blockade-induced pulmonary hypertension that characterizes the SU5416-hypoxia rat model of PAH and attempt to translate the knowledge gained from the experimental model to the human disease by postulating the potential role of endogenous (SU5416-like) VEGF inhibitors. The main objective of this review is to promote discussion and investigation of the opposing and complementary actions of VEGF in PAH. Understanding the balance between angiogenic and anti-angiogenic factors and their role in the pathogenesis of PAH will be necessary before anti-angiogenic drugs can be considered for the treatment of PAH.