Abstract
Ageing is associated with endothelial dysfunction, decreased endothelial progenitor cell (EPC) function and mobilization. These defects culminate in a decreased capacity for neovascularization in the aged. Multiple lines of evidence suggest that defective neovascularization with ageing is related to depressed signaling by hypoxia inducible factor-1 (HIF-1). HIF-1, the master regulator or neovascularization, regulates the expression of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and CXC chemokine Receptor-4 (CXCR4). Given that the SDF-1/CXCR4 axis is a crucial regulator of progenitor cell function and homing, the ramifications of depressed HIF-1 signaling with age include depressed vascular repair, neovascularization and wound healing. We review the literature showing the depression of these processes with age and discuss the relevance of these findings to several clinical contexts. Further, the effects of age on EPC number, function and mobilization are related to the age-related decline in HIF-1 signaling. We suggest that exercise, Cobalt compounds or hydralazine may reverse the age-related decline by up-regulating HIF-1- mediated signaling.
Keywords: Endothelial progenitor cell, angiogenesis, neovascularization, hypoxia inducible factor, stromal cell derived factor-1, ageing, exercise
Current Molecular Medicine
Title: Decreased Vascular Repair and Neovascularization with Ageing: Mechanisms and Clinical Relevance with an Emphasis on Hypoxia- Inducible Factor-1
Volume: 8 Issue: 8
Author(s): Michel R. Hoenig, Cesario Bianchi, Anthony Rosenzweig and Frank W. Sellke
Affiliation:
Keywords: Endothelial progenitor cell, angiogenesis, neovascularization, hypoxia inducible factor, stromal cell derived factor-1, ageing, exercise
Abstract: Ageing is associated with endothelial dysfunction, decreased endothelial progenitor cell (EPC) function and mobilization. These defects culminate in a decreased capacity for neovascularization in the aged. Multiple lines of evidence suggest that defective neovascularization with ageing is related to depressed signaling by hypoxia inducible factor-1 (HIF-1). HIF-1, the master regulator or neovascularization, regulates the expression of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and CXC chemokine Receptor-4 (CXCR4). Given that the SDF-1/CXCR4 axis is a crucial regulator of progenitor cell function and homing, the ramifications of depressed HIF-1 signaling with age include depressed vascular repair, neovascularization and wound healing. We review the literature showing the depression of these processes with age and discuss the relevance of these findings to several clinical contexts. Further, the effects of age on EPC number, function and mobilization are related to the age-related decline in HIF-1 signaling. We suggest that exercise, Cobalt compounds or hydralazine may reverse the age-related decline by up-regulating HIF-1- mediated signaling.
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Cite this article as:
Hoenig R. Michel, Bianchi Cesario, Rosenzweig Anthony and Sellke W. Frank, Decreased Vascular Repair and Neovascularization with Ageing: Mechanisms and Clinical Relevance with an Emphasis on Hypoxia- Inducible Factor-1, Current Molecular Medicine 2008; 8 (8) . https://dx.doi.org/10.2174/156652408786733685
DOI https://dx.doi.org/10.2174/156652408786733685 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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