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Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17

(2012) CIRCULATION RESEARCH. 111(12). p.1539-1550
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Organization
Abstract
Rationale: The density of native (preexisting) collaterals varies widely and is a significant determinant of variation in severity of stroke, myocardial infarction, and peripheral artery disease. However, little is known about mechanisms responsible for formation of the collateral circulation in healthy tissues. Objective: We previously found that variation in vascular endothelial growth factor (VEGF) expression causes differences in collateral density of newborn and adult mice. Herein, we sought to determine mechanisms of collaterogenesis in the embryo and the role of VEGF in this process. Methods and Results: Pial collaterals begin forming between embryonic day 13.5 and 14.5 as sprout-like extensions from arterioles of existing cerebral artery trees. Global VEGF-A overexpressing mice (Vegf(hi/+)) formed more, and Vegf(lo/+) formed fewer, collaterals during embryogenesis, in association with differences in vascular patterning. Conditional global reduction of Vegf or Flk1 only during collaterogenesis significantly reduced collateral formation, but now without affecting vascular patterning, and the effects remained in adulthood. Endothelial-specific Vegf reduction had no effect on collaterogenesis. Endothelial-specific reduction of a disintegrin-and-metalloprotease-domain-10 (Adam10) and inhibition of gamma-secretase increased collateral formation, consistent with their roles in VEGF-induced Notch1 activation and suppression of prosprouting signals. Endothelial-specific knockdown of Adam17 reduced collateral formation, consistent with its roles in endothelial cell migration and embryonic vascular stabilization, but not in activation of ligand-bound Notch1. These effects also remained in adulthood. Conclusions: Formation of pial collaterals occurs during a narrow developmental window via a sprouting angiogenesis-like mechanism, requires paracrine VEGF stimulation of fetal liver kinase 1-Notch signaling, and adult collateral number is dependent on embryonic collaterogenesis.
Keywords
MICE, ADAM10, EXPRESSION, ANGIOGENESIS, vascular endothelial growth factor, embryo, collateral, angiogenesis, a disintegrin and metalloprotease, FLOW, BRAIN, ALPHA CONVERTING-ENZYME, CELL PROLIFERATION, ARTERIAL IDENTITY, CHICK-EMBRYO

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Citation

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MLA
Lucitti, Jennifer L, Jessica K Mackey, Jeffrey C Morrison, et al. “Formation of the Collateral Circulation Is Regulated by Vascular Endothelial Growth factor-A and a Disintegrin and Metalloprotease Family Members 10 and 17.” CIRCULATION RESEARCH 111.12 (2012): 1539–1550. Print.
APA
Lucitti, J. L., Mackey, J. K., Morrison, J. C., Haigh, J., Adams, R. H., & Faber, J. E. (2012). Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17. CIRCULATION RESEARCH, 111(12), 1539–1550.
Chicago author-date
Lucitti, Jennifer L, Jessica K Mackey, Jeffrey C Morrison, Jody Haigh, Ralf H Adams, and James E Faber. 2012. “Formation of the Collateral Circulation Is Regulated by Vascular Endothelial Growth factor-A and a Disintegrin and Metalloprotease Family Members 10 and 17.” Circulation Research 111 (12): 1539–1550.
Chicago author-date (all authors)
Lucitti, Jennifer L, Jessica K Mackey, Jeffrey C Morrison, Jody Haigh, Ralf H Adams, and James E Faber. 2012. “Formation of the Collateral Circulation Is Regulated by Vascular Endothelial Growth factor-A and a Disintegrin and Metalloprotease Family Members 10 and 17.” Circulation Research 111 (12): 1539–1550.
Vancouver
1.
Lucitti JL, Mackey JK, Morrison JC, Haigh J, Adams RH, Faber JE. Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17. CIRCULATION RESEARCH. 2012;111(12):1539–50.
IEEE
[1]
J. L. Lucitti, J. K. Mackey, J. C. Morrison, J. Haigh, R. H. Adams, and J. E. Faber, “Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17,” CIRCULATION RESEARCH, vol. 111, no. 12, pp. 1539–1550, 2012.
@article{3083151,
  abstract     = {Rationale: The density of native (preexisting) collaterals varies widely and is a significant determinant of variation in severity of stroke, myocardial infarction, and peripheral artery disease. However, little is known about mechanisms responsible for formation of the collateral circulation in healthy tissues. 
Objective: We previously found that variation in vascular endothelial growth factor (VEGF) expression causes differences in collateral density of newborn and adult mice. Herein, we sought to determine mechanisms of collaterogenesis in the embryo and the role of VEGF in this process. 
Methods and Results: Pial collaterals begin forming between embryonic day 13.5 and 14.5 as sprout-like extensions from arterioles of existing cerebral artery trees. Global VEGF-A overexpressing mice (Vegf(hi/+)) formed more, and Vegf(lo/+) formed fewer, collaterals during embryogenesis, in association with differences in vascular patterning. Conditional global reduction of Vegf or Flk1 only during collaterogenesis significantly reduced collateral formation, but now without affecting vascular patterning, and the effects remained in adulthood. Endothelial-specific Vegf reduction had no effect on collaterogenesis. Endothelial-specific reduction of a disintegrin-and-metalloprotease-domain-10 (Adam10) and inhibition of gamma-secretase increased collateral formation, consistent with their roles in VEGF-induced Notch1 activation and suppression of prosprouting signals. Endothelial-specific knockdown of Adam17 reduced collateral formation, consistent with its roles in endothelial cell migration and embryonic vascular stabilization, but not in activation of ligand-bound Notch1. These effects also remained in adulthood. 
Conclusions: Formation of pial collaterals occurs during a narrow developmental window via a sprouting angiogenesis-like mechanism, requires paracrine VEGF stimulation of fetal liver kinase 1-Notch signaling, and adult collateral number is dependent on embryonic collaterogenesis.},
  author       = {Lucitti, Jennifer L and Mackey, Jessica K and Morrison, Jeffrey C and Haigh, Jody and Adams, Ralf H and Faber, James E},
  issn         = {0009-7330},
  journal      = {CIRCULATION RESEARCH},
  keywords     = {MICE,ADAM10,EXPRESSION,ANGIOGENESIS,vascular endothelial growth factor,embryo,collateral,angiogenesis,a disintegrin and metalloprotease,FLOW,BRAIN,ALPHA CONVERTING-ENZYME,CELL PROLIFERATION,ARTERIAL IDENTITY,CHICK-EMBRYO},
  language     = {eng},
  number       = {12},
  pages        = {1539--1550},
  title        = {Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17},
  url          = {http://dx.doi.org/10.1161/CIRCRESAHA.112.279109},
  volume       = {111},
  year         = {2012},
}

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