Prolonged hypoxia also induces the transcription factor HIF1A, which directly activates downstream growth factor signaling that causes irreversible proliferation and remodeling of pulmonary arterial endothelial cells, leading to chronic pulmonary arterial hypertension.In CTEPH (WHO Group IV), the initiating event is thought to be blockage or narrowing of the pulmonary blood vessels with unresolved blood clots; these clots can lead to increased pressure and shear stress in the rest of the pulmonary circulation, precipitating structural changes in the vessel walls (remodeling) similar to those observed in other types of severe pulmonary hypertension. This combination of vessel occlusion and vascular remodeling once again increases the resistance to blood flow and so the pressure within the system rises. Molecular pathology
The molecular mechanism of pulmonary arterial hypertension (PAH) is not known yet, but it is believed that the endothelial dysfunction results in a decrease in the synthesis of endothelium-derived vasodilators such as nitric oxide and prostacyclin. Moreover, there is a stimulation of the synthesis of vasoconstrictors such as thromboxane and vascular endothelial growth factor (VEGF). These result in a severe vasoconstriction and vascular smooth muscle  and adventitial hypertrophy characteristic of patients with PAH. Nitric oxide-soluble guanylate cyclase pathway
In normal conditions, the vascular endothelial nitric oxide synthase produces nitric oxide from L-arginine in the presence of oxygen.This nitric oxide diffuses into neighboring cells (including vascular smooth muscle cells and platelets), where it increases the activity of the enzyme soluble guanylate cyclase, leading to increased formation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP).
In systemic scleroderma, the incidence has been estimated to be 8 to 12% of all patients; in rheumatoid arthritis it is rare. However, in systemic lupus erythematosus it is 4 to 14%, and in sickle cell disease, it ranges from 20 to 40%. Up to 4% of people who develop a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension. A small percentage of patients with COPD develop pulmonary hypertension with no other disease to explain the high pressure. On the other hand, obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension. Research
For people that inherited the disease, gene therapy is being studied. Notable cases
Elaine Kaufman, American restaurateur
Ina Balin, American Broadway and TV actress
Chloe Temtchine, American singer-songwriter
Natalie Cole, American singer

See also
Pulmonary Hypertension Association
Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)

References
Further reading
Rubin LJ, Badesch DB (August 2005). "Evaluation and management of the patient with pulmonary arterial hypertension". Annals of Internal Medicine. 143 (4): 282–92. CiteSeerX 10.1.1.463.8466. doi:10.7326/0003-4819-143-4-200508160-00009. PMID 16103472. S2CID 28841269. Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK,  et al. (November 2015). "Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society". Circulation. 132 (21): 2037–99. doi:10.1161/CIR.0000000000000329. PMID 26534956. S2CID 7412370. External links
The Merck Manual Home Edition: Pulmonary Hypertension