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Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Pulmonary Hypertension: Current Therapy and Future Prospects

Author(s): Rajamma Mathew

Volume 9, Issue 3, 2011

Page: [165 - 182] Pages: 18

DOI: 10.2174/187152511797037501

Price: $65

Abstract

Pulmonary hypertension (PH) is a sequel of a variety of cardiovascular and systemic diseases. Heterozygous mutation of BMPRII, a member of the TGFβ superfamily is the commonest genetic defect so far identified in PH. Recent advances have contributed a great deal to the understanding of the disease; however, the actual mechanism/s is not yet clear. Endothelial damage is the key underlying feature of PH. The main effects are loss of vascular relaxation response, increased cell proliferation and impaired apoptosis, matrix deposition, obstruction in the small pulmonary arteries, right ventricular hypertrophy; and eventually leading to right heart failure and death. The diagnosis of PH is often made late because of the insidious onset of symptoms, therefore the treatment poses a daunting challenge. Furthermore, depending on the underlying pathology, not all patients respond equally to same therapeutic agents. Current therapy includes a group of drugs mainly involved in improving vascular relaxation (cAMP and cGMP mechanisms) and endothelin receptor blockers alone or in combination. Newer drugs such as guanylate cyclase activators, PDGF blocker, RhoA/Rho kinase blockers have shown encouraging results in animal studies and in a few clinical cases of PH. Other drugs and signaling pathways such as nitrite, PPARγ, ACE2, ghrelin etc. are under investigation. Studies with gene therapy are being actively pursued. This review summarizes the available therapy and the future prospects.

Keywords: ACE2, anti-oxidants, endothelin-1 receptor blockers, gene therapy, micro RNAs, nitrite, PDGF, phosphodiesterase inhibitors, PPAR gamma, prostacyclin, RhoA/ROCK, serotonin, sGC activators, statins, VIP


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