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Mechanisms Underlying Coronary Collateral Growth
Author(s) -
Chilian William M,
Rocic Petra
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a79-d
Subject(s) - collateral , medicine , vascular endothelial growth factor , growth factor , collateral circulation , cardiology , receptor , vegf receptors , finance , economics
Coronary collateral growth has the potential to impact significantly the clinical outcome of patients with ischemic heart disease. Despite several clinical trials that were designed to stimulate collateral growth in the heart, there is a paucity of knowledge about the causal mechanisms underlying this process, and the mechanisms underlying the abrogated development of collaterals in models of pathology. To this end we have developed a rat model of coronary collateral development that enables delineation of the cause and effect roles of different growth factors, and engenders the study of genetic models of pathology, e.g., obesity and prediabetes. Our work to date has shown the pivotal role for vascular endothelial growth factor (VEGF) in coronary collateral development because administration of neutralizing antibodies against VEGF block the vascular growth. Interestingly in a model of the metabolic syndrome characterized by insulin resistance and obesity (Zucker obese fatty rat, ZOF), gene therapy using intracoronary smooth muscle cells to carry VEGF does not improve coronary collateral growth, suggesting that this growth factor alone cannot rectify collateral growth in the heart. However, administration of VEGF and ecSOD in the ZOF rat partially restores collateral growth. This observation suggests that in addition to VEGF, recitification of oxidative stress must also accompany growth factor therapy in models of vascular disease and oxidative stress. Undoubtedly the process of coronary collateral growth is caused by myriad signals and growth factors, but of the many, redox signaling and VEGF appear to be requisites for this adaptive process.