Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension

Jeffery, T.K. and Wanstall, J.C. (2001) Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension. Pharmacology & Therapeutics, 92 1: 1-20. doi:10.1016/S0163-7258(01)00157-7

Author Jeffery, T.K.
Wanstall, J.C.
Title Pulmonary vascular remodeling: a target for therapeutic intervention in pulmonary hypertension
Journal name Pharmacology & Therapeutics   Check publisher's open access policy
ISSN 0163-7258
Publication date 2001-10-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/S0163-7258(01)00157-7
Open Access Status Not yet assessed
Volume 92
Issue 1
Start page 1
End page 20
Total pages 20
Editor A.C. Sartorelli
W.C. Bowman
Place of publication Oxford, England
Publisher Elsevier Science
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Abstract Pulmonary vascular remodeling is an important pathological feature of pulmonary hypertension, leading to increased pulmonary vascular resistance and reduced compliance. It involves thickening of all three layers of the blood vessel wall (due to hypertrophy and/or hyperplasia of the predominant cell type within each layer), as well as extracellular matrix deposition. Neomuscularisation of non-muscular arteries and formation of plexiform and neointimal lesions also occur. Stimuli responsible for remodeling involve transmural pressure, stretch, shear stress, hypoxia, various mediators [angiotensin II, endothelin (ET)-1, 5-hydroxytryptamine, growth factors, and inflammatory cytokines], increased serine elastase activity, and tenascin-C. In addition, there are reductions in the endothelium-derived antimitogenic substances, nitric oxide, and prostacyclin. Intracellular signalling mechanisms involved in pulmonary vascular remodeling include elevations in intracellular Ca2+ and activation of the phosphatidylinositol pathway, protein kinase C, and mitogen-activated protein kinase. In animal models of pulmonary hypertension, various drugs have been shown to attenuate pulmonary vascular remodeling. These include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, ET receptor antagonists, ET-converting enzyme inhibitors, nitric oxide, phosphodiesterase 5 inhibitors, prostacyclin, Ca2+-channel antagonists, heparin, and serine elastase inhibitors. Inhibition of remodeling is generally accompanied by reductions in pulmonary artery pressure. The efficacy of some of the drugs varies, depending on the animal model of the disease. In view of the complexity of the remodeling process and the diverse aetiology of pulmonary hypertension in humans, it is to be anticipated that successful anti-remodeling therapy in the clinic will require a range of different drug options. (C) 2001 Elsevier Science Inc. All rights reserved.
Keyword Pharmacology & Pharmacy
Pulmonary Vascular Remodeling
Pulmonary Hypertension
Anti-remodeling Drugs
Pulmonary Blood Vessels
Smooth-muscle Cells
Right-ventricular Hypertrophy
Endothelial Growth-factor
Chronically Hypoxic Rats
Eta-receptor Antagonist
Serine Elastase Inhibitor
Congenital Heart-defects
Inhaled Nitric-oxide
Q-Index Code C1

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 196 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 15 Aug 2007, 01:03:51 EST