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Novel and Emerging Therapies for Pulmonary Hypertension.
Am J Respir Crit Care Med. 2014 Jan 8;
Authors: Pullamsetti SS, Schermuly R, Ghofrani A, Weissmann N, Grimminger F, Seeger W
Abstract
The development of therapeutic concepts in pulmonary hypertension 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 pulmonary hypertension. 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. Anti-proliferative strategies, transcription factor-based therapies, inflammation/immune cell-focused approaches, and epigenetic modulation-based therapies are all novel treatment concepts for pulmonary hypertension. The pro-angiogenic 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 pulmonary hypertension. However, understanding the molecular sequelae underlying pulmonary hypertension in groups 2-5 pulmonary hypertension is also urgently needed.
PMID: 24401129 [PubMed - as supplied by publisher]