In primary pulmonary hypeension basic abnormality in genelies in-

Vasoconstriction, vascular proliferation, thrombosis, and inflammation appear to underlie the development of PAH ( Fig. 250-2 ). Abnormalities in multiple molecular pathways and genes that regulate the pulmonary vascular endothelial and smooth muscle cells have been identified. These abnormalities include decreased expression of the voltage-regulated potassium channel, mutationsin the BONE MORPHOGENETIC PROTEIN -2 RECEPTOR , increased tissue factor expression, overactivation of the serotonin transpoer, trans cription factor activation of hypoxia-inducible factor-1 alpha, and activation of nuclear factor of activated T cells. As a result, there appears to be loss of apoptosis of the smooth muscle cells that allows their proliferation and the emergence of apoptosisresistant endothelial cells that can obliterate the vascular lumen. In addition, thrombin deposition in the pulmonary vasculature from a procoagulant state that develops as an independent abnormality or as a result of endothelial dysfunction may amplify the vascular proliferation. ref:Harrison&;s principles of internal medicine,ed 18,pg no 2077