Transitional angiogenesis and vascular remodeling during coronary angiogenesis in response to myocardial infarction.
Coronary artery disease (CAD) is a major source of morbidity and mortality in the industrialized world. CAD causes ischemia as a prelude to angina, myocardial infarction and heart failure as specific forms of heart disease causing a decline in the quality of life. CAD or atherosclerosis and the resulting myocardial ischemia trigger a natural angiogenic response that generates collateral circulations. The long-term goal for these studies is to develop therapeutic angiogenesis that augments the natural coronary angiogenesis. This project makes use of an infarcted transgenic mouse model to characterize formation of those collateral circulations in the post-infraction heart. The experiments utilized thoracotomy and a microcauterizer to produce an infarct in transgenic mice and this stimulated neovascularization and allowed labeling of the coronary vessels, thereby defining the morphogenic processes involved in formation of collateral circulations. The results show that the heart consistently responds to infarcts with angiogenesis at 1d post-treatment (PT) that undergoes transition into vascular remodeling at 7d PT with complete remodeling at 14d PT. The vascular remodeling appears to mitigate any net increase in perfusion that may be achieved early in coronary angiogenesis. The results suggest that therapeutic approaches need to shift from an exclusive focus on stimulating angiogenesis to include modulation of vascular remodeling for increased long-term myocardial perfusion.
Grass
Taren M
TM
Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, SB244, The University of Montana, Missoula, MT 59812, USA.
Lurie
Diana I
DI
Coffin
J Douglas
JD
D000199:Actins / Q000032:analysis; D000818:Animals; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D018919:Neovascularization, Physiologic; D013194:Staining and Labeling / Q000379:methods; D020257:Ventricular Remodeling
D000199:Actins