Novel Therapeutic Targets of Pulmonary Hypertension
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- AMP-activated kinase
- heart failure
- pulmonary hypertension
- rho-associated kinase
- thrombin-activatable fibrinolysis inhibitor
Pulmonary hypertension (PH) is a fatal disease caused by small pulmonary artery obstruction by vascular proliferation and remodeling.1 PH is characterized by elevated pulmonary arterial pressure and increased pulmonary vascular resistance, frequently leading to right heart failure and death. PH is defined as a mean pulmonary arterial pressure ≥25 mm Hg at rest with right heart catheterization.2
The classification of PH includes 5 major categories of the disorder.2 Group 1, which is called as pulmonary arterial hypertension (PAH), is a clinical condition defined as mean pulmonary arterial pressure ≥25 mm Hg and pulmonary capillary wedge pressure ≤15 mm Hg, which is characterized by the presence of precapillary PH in the absence of other causes of precapillary PH, such as PH caused by lung diseases, chronic thromboembolic PH (CTEPH), or other rare diseases. Pulmonary veno-occlusive diseases and pulmonary capillary hemangiomatosis (Group 1) are caused by occlusion of pulmonary vein and should be a distinct category. These diseases are not completely separated from PAH because they share similar characteristics with PAH. Group 2 PH is caused by left heart disease, which is characterized by the passive backward transmission of the pressure elevation (postcapillary PH). Group 3 PH is caused by lung diseases and hypoxia, which is caused by hypoxic vasoconstriction as a result of lung diseases. Group 4 PH is called as CTEPH, which is caused by chronic and mechanical obstruction of central and distal pulmonary arteries by organized thrombi. Group 5 PH is caused by rare diseases, such as sarcoidosis and aortitis.
Although the treatment of PH has been developed, including prostaglandin I2,3 endothelin receptor antagonists,4 phosphodiesterase V inhibitor,5 and soluble guanylate cyclase,6 PH still remains a fatal disease. Thus, the novel therapeutic targets for PH remain to be elucidated. Indeed, significant progresses have been …