Prostacyclin therapy for pulmonary arterial hypertension.
In pulmonary arterial hypertension, the blood vessels that carry blood between the heart and lungs are constricted, making it difficult for the heart to pump blood through the lungs. Prostacyclin, a prostanoid metabolized from endogenous arachidonic acid through the cyclooxygenase (COX) pathway, is a potent vasodilator that has been identified as one of the most effective drugs for the treatment of pulmonary arterial hypertension. Currently, prostacyclin and its analogues are widely used in the clinical management of pulmonary arterial hypertension patients. However, the mortality rate associated with pulmonary arterial hypertension has not been significantly reduced within the past 5 years. More powerful therapeutic approaches are needed. This article briefly reviews the current management of pulmonary arterial hypertension to identify the problems associated with present therapies; then it focuses on the emerging technology of prostacyclin synthase gene therapy and cell-based therapy using native stem cells and engineered stem cells with enhanced prostacyclin production capacity. By using the recent advances in technology and the molecular understanding of prostacyclin synthesis, researchers are prepared to make significant advances in the treatment of pulmonary arterial hypertension.
Ruan
Cheng-Huai
CH
Department of Internal Medicine, New York Hospital Medical Center of Queens/Weil Cornell Medical College Affiliated Hospital, Flushing, New York 11355, USA. chr9062@nyp.org
Dixon
Richard A F
RA
Willerson
James T
JT
Ruan
Ke-He
KH
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D011464:Epoprostenol / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase