International journal of cardiology
-
Most patients with severe pulmonary arterial hypertension (PAH) demonstrate persistent structural alterations in small pulmonary arterioles at the time of diagnosis, including marked proliferation of pulmonary artery endothelial cells (ECs), smooth muscle cells (SMCs) and fibroblasts. Rai et al. have recently proposed a paradigm shift to explain the pathobiology of small vessel disease in severe PAH patients as a quasi-neoplastic process. Indeed, the vascular lesions of patients with severe PAH exhibit some cancer-like characteristics: decreased population of apoptotic cells and overexpression of antiapoptotic proteins. ⋯ PDGF has been identified as a novel potential therapeutic target and the successful treatment of experimental PAH with a PDGF receptor tyrosine kinase inhibitor has been demonstrated recently. These findings justify further clinical trials concerning thyrosine kinase inhibitors as future PAH therapies. However, the drugs currently developed for malignant neoplasms to target neoplastic proliferation should be tested carefully in PAH patients due to their cardiac and pulmonary toxicity.