title: Matrix metalloproteinases and their inhibitors in pulmonary hypertension.
abstract: Pulmonary hypertension (PH) is a severe and progressive disease characterised by high pulmonary artery pressure, usually culminating in right heart failure. Current therapeutic approaches in PH largely provide symptomatic relief while the prognosis rate is lower due to the lack of specific molecular targets and the involvement of several factors in the development of PH. Numerous studies have suggested a crucial role of matrix metalloproteinase (MMP) axis during development and disease states, specifically with regard to extracellular matrix remodelling and vascular homeostasis. Increased MMP activity has been demonstrated in experimental animal models of PH, and MMP inhibition has been shown to either attenuate or enhance vascular remodelling. Moreover, several studies emphasise that restoration of deregulated MMPs to physiological MMP/tissue inhibitor of MMPs ratios would potentiate reverse remodelling in PH. This article will highlight the pathophysiological role of MMPs in vascular remodelling and the establishment of PH. In particular, we will focus on the MMP expression and regulation in pulmonary vasculature and pulmonary vascular remodelling. We will also provide an overview of recent clinical and experimental findings and their impact on achieving maximum reversal of PH, as well as current issues and future perspectives.
authors.affiliation: Max-Planck-Institute for Heart and Lung Research, Parkstrasse-1, 61231-Bad Nauheim, Germany.
authors.forename: Prakash
authors.initials: P
authors.lastname: Chelladurai
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Soni Savai
authors.initials: SS
authors.lastname: Pullamsetti
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D016686:Monocrotaline / Q000494:pharmacology; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D016686:Monocrotaline; D020782:Matrix Metalloproteinases