Targeting Vessel Formation in Pulmonary Arterial Hypertension: Is the Endostatin- Id1 -Thrombospondin 1 Pathway a New Hope?

Pulmonary endothelial dysfunction is a characteristic of pulmonary arterial hypertension (PAH) and is believed to be an early event that determines many of the other key pathological processes in the development of this devastating condition. Pathways involved in the regulation of blood vessel formation and repair are relevant to the formation of pulmonary vascular lesions and restoration of distal pulmonary perfusion in PAH. Thus, established angiopoietic and angiostatic factors have been a focus of targeted research studies in recent years. A decade ago, Kumpers and colleagues reported finding elevated circulating concentrations of angiopoietin 1 and its inhibitor angiopoietin 2 in a study of 104 patients with idiopathic PAH. Angiopoietin 2 alone was prognostic of, and expression in patient lung tissues was associated with, the formation of plexogenic lesions, where it might function to destabilize established vessels at initiation of remodeling. A more recent study confirmed the lack of association between circulating angiopoietin 1 and outcomes in patients with pulmonary hypertension, with no differences in etiologies, including connective tissue disease, left heart dysfunction, and chronic thromboembolic disease-associated forms of pulmonary hypertension.