title: 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.affiliation: 1 Max-Planck-Institute for Heart and Lung Research, Department of Lung Development and Remodeling, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany; and.
authors.forename: Soni Savai
authors.initials: SS
authors.lastname: Pullamsetti
authors.forename: Ralph
authors.initials: R
authors.lastname: Schermuly
authors.forename: Ardeschir
authors.initials: A
authors.lastname: Ghofrani
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D044127:Epigenesis, Genetic; D065627:Familial Primary Pulmonary Hypertension; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D014664:Vasodilation; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D000959:Antihypertensive Agents; D056572:Histone Deacetylase Inhibitors; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D013449:Sulfonamides; D014665:Vasodilator Agents; C542595:riociguat; C533860:macitentan