Pulmonary Arterial Hypertension: Molecular Genetic Basis and Emerging Treatments

PAH is caused by the obstruction of pulmonary arteries due to excessive proliferation of cells in tunica intima, tunica media and tunica adventitia along with deposition of components of extracellular matrix. The formation of occlusive lesion initiates in the tunica media, called as medial thickening, as the pulmonary arterial smooth muscle cells (PASMCs) start to proliferate. Medial thickening is followed by the proliferation of endothelial cells and transitional cells in the tunica intima and fibroblasts in the tunica adventitia. Intimal thickening occurs in two phases, initially myofibroblast like cells, originating from the PASMCs, migrate to the endothelial lining and start dividing and then the collagen deposition occurs. However, in the most severe occlusions, plexiform lesions are formed Pulmonary arterial hypertension (PAH) is a rare cardiovascular disorder characterised by the sustained elevation of blood pressure in pulmonary arteries, recorded above 25 mm of Hg during rest and 30 mm of Hg during exercise1. The rise in the pressure occurs due to occlusion of pulmonary arteries in the lungs leading to subsequent right heart failure and death, if left untreated. It is estimated that approximately 146,000 subjects suffer from this devastating disease across the EU, USA and Japan. Although the cases of PAH have been reported in India, Pakistan and Bangladesh yet a lack of epidemiology accounts for the unavailability of PAH patients in the Indian subcontinent2.