Abstract 16163: Foxc2 is Required for Neovascularization During Ischemic Tissue Repair After Myocardial Infarction
Rationale: The Foxc2 transcription factor has been implicated in vascular development. We have recently demonstrated that Foxc2 is an important regulator of tumor angiogenesis; however, the role of Foxc2 in pathological neovascularization involving ischemic conditions remains largely unknown. We hypothesized that Foxc2 is critical for neovascularization and ischemic tissue repair after myocardial infarction (MI).
Objective: To investigate the function of Foxc2 in pathological neovascularization during ischemic tissue repair after MI.
Methods and Results: To determine the effects of hypoxia on regulation of Foxc2, we first tested whether Foxc2 expression is regulated by hypoxia. We found that levels of Foxc2 mRNA were transiently increased in human umbilical vein endothelial cells (HUVECs) 1 hour after hypoxia induction in vitro. Consistently, expression of Foxc2 was acutely upregulated in ischemic myocardial tissue of murine hearts 1 day after surgically induced MI. We next examined whether Foxc2 deficiency can influence neovascularization and cardiac repair after MI. Echocardiographic measurements of left ventricular ejection fractions and fractional shortening were reduced in heterozygous Foxc2 null mutant (Foxc2+/-) mice after MI compared to wild-type mice, whereas cardiac fibrosis was increased in Foxc2+/- mice. Most significantly, Foxc2+/- mice had a drastic reduction in capillary vessel formation in the ischemic border zone after MI compared to wild-type mice.
Conclusions: Foxc2 is transiently induced in vascular endothelial cells in vitro under hypoxia and in ischemic murine hearts after MI, and is required for neovascularization during ischemic tissue repair after MI.
- © 2011 by American Heart Association, Inc.