Novel and emerging therapies for pulmonary hypertension.

Abstract

The development of therapeutic concepts in pulmonary hypertension (PH) is intimately linked with the unraveling of pathogenetic sequelae. This perspective highlights advances in our understanding of the regulation of vasomotion and vascular remodeling that have led to "reverse-remodeling" and regenerative strategies as novel treatment concepts. Progress has been made in understanding redox-dependent signaling; inflammatory sequelae; and transcription factor, ion channel, and metabolic abnormalities, as well as growth factor-dependent hyperproliferation that underlies PH. We are, however, far from understanding the molecular pathways that differentially drive the various vascular phenotypes (intimal thickening, media hypertrophy, adventitial thickening, plexiform lesions, vascular pruning) in this disease. Antiproliferative strategies, transcription factor-based therapies, inflammation/immune cell-focused approaches, and epigenetic modulation-based therapies are all novel treatment concepts for PH. The proangiogenic potential of genetically engineered mesenchymal stem cells and endothelial progenitor cells has been explored as a regenerative strategy. The progress that has been made in identifying important cellular and molecular mechanisms and applying this knowledge to novel therapies is largely restricted to group 1 PH. However, understanding the molecular sequelae underlying PH in groups 2 through 5 PH is also urgently needed.

• Authors: Soni Savai Pullamsetti, Ralph Schermuly, Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 189 Issue 4 Pg. 394-400 (Feb 15 2014) ISSN: 1535-4970 [Electronic] United States
• PMID: 24401129 (Publication Type: Journal Article, Review)

Chemical References

• Angiogenesis Inhibitors
• Antihypertensive Agents
• Histone Deacetylase Inhibitors
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• Sulfonamides
• Vasodilator Agents
• riociguat
• macitentan

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Epigenesis, Genetic
• Familial Primary Pulmonary Hypertension
• Histone Deacetylase Inhibitors (therapeutic use)
• Humans
• Hypertension, Pulmonary (drug therapy, genetics, immunology, physiopathology)
• Protein Kinase Inhibitors (therapeutic use)
• Pulmonary Artery (physiopathology)
• Pyrazoles (therapeutic use)
• Pyrimidines (therapeutic use)
• Sulfonamides (therapeutic use)
• Vasodilation
• Vasodilator Agents (therapeutic use)