Pulmonary Arterial Hypertension and Cancer: An Update on Their Similarities

Abstract

Pulmonary arterial hypertension (PAH) is characterized by an increase resistance of the vascular wall from pulmonary arteries leading to vascular lumen occlusion, right ventricular failure, and death. PAH has been described for many years, as a cardiovascular disease affecting the lungs. Whatever the initial cause, pulmonary arterial hypertension involves the vasoconstriction of blood vessels connected to and within the lungs. In addition, the increased workload of the heart causes hypertrophy of the right ventricle, making the heart less able to pump blood through the lungs, causing right heart failure. Recently several groups have demonstrated that PAH is a disease of excess proliferation and impaired apoptosis similar to neoplasia. Although the fundamental cause remains elusive, many predisposing and disease-modifying abnormalities occur, including endothelial injury/dysfunction, bone morphogenetic protein receptor-2 gene mutations, decreased expression of the K+ channel (Kv1.5), transcription factor activation [hypoxia-inducible factor-1 (HIF-1 )], expression of survivin, and increased expression/activity of both serotonin transporters and platelet-derived growth factor receptors. Together, these abnormalities create a cancer-like, proliferative, apoptosis-resistant phenotype. From these observations, it has been established some similarities between PAH and cancer. Therefore, in this review, we will discuss the essential alterations in pulmonary arterial hypertension as compared to cancer cell which has been alluded to as the “cancer paradigm”. Based on these similarities, we can imagine that future therapies used to treat cancer could also work for PAH.