Authors: Makinde, Toluwalope; Murphy, Richard F.; Agrawal, Devendra K.

Source: Current Molecular Medicine, Volume 6, Number 8, December 2006 , pp. 831-841(11)

Publisher: Bentham Science Publishers

Abstract:

The blood vessels formed in asthmatic airways are involved in inflammatory and airway remodeling processes in chronic asthma. Vascular endothelial cell growth factor (VEGF) and angiopoietin-1 (Ang-1) are primary angiogenic growth factors, involved in the formation of such blood vessels. VEGF has been reported to contribute to non-specific airway hyper-responsiveness, have chemotactic effects on eosinophils, and enhance airway smooth muscle cell proliferation. Furthermore, Th2 cells have receptors for VEGF, and Th2-associated cytokines increase VEGF production. There are reports that elevated levels of VEGF correlates with the severity of asthma. Ang-1 has been shown to induce pro-inflammatory effects such as eosinophil chemotaxis via tie-2 receptors. Reports indicate ang-1 contribution to increased secretion of matrix metalloproteinase-2 (MMP-2) and decreased secretion of tissue inhibitors of metalloproteinase-2 (TIMP-2). However, Ang-1 has also been shown to exhibit several anti-inflammatory properties such as suppressing expression of adhesion molecules, blocking vascular permeability and eosinophil chemotaxis induced by VEGF. These findings support the notion that apart from their roles in blood vessels formation, these angiogenic growth factors are directly involved in the pathogenesis of chronic asthma. This paper reviews individual and combined roles of VEGF and Ang-1. The potential therapeutic applications involving these factors are also discussed.

Keywords: Airway Remodeling; angiopoietin-1; asthma; chronic asthma; vascular endothelial growth factor

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156652406779010795

Affiliations: 1: Professor of Biomedical Sciences, Medicine, and Medical Microbiology and Immunology,Creighton University School of Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE 68178, USA.

Publication date: 2006-12-01

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• Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.

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