title: Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues.
abstract: OBJECTIVE
  Aging is a major risk factor for increased ischemic tissue injury. Whether collateral rarefaction and impaired remodeling contribute to this is unknown. We quantified the number and diameter of native collaterals and their remodeling in 3-, 16-, 24-, and 31-month-old mice.
  
  
  RESULTS
  Aging caused an "age-dose-dependent" greater drop in perfusion immediately after femoral artery ligation, followed by a diminished recovery of flow and increase in tissue injury. These effects were associated with a decline in collateral number, diameter, and remodeling. Angiogenesis was also impaired. Mechanistically, these changes were not accompanied by reduced recruitment of T cells or macrophages to remodeling collaterals. However, endothelial nitric oxide synthase signaling was dysfunctional, as indicated by increased protein nitrosylation and less phosphorylated endothelial nitric oxide synthase and vasodilator-stimulated phosphoprotein in collateral wall cells. The cerebral circulation exhibited a similar age-dose-dependent loss of collateral number and diameter and increased tortuosity, resulting in an increase in collateral resistance and infarct volume (eg, 6- and 3-fold, respectively, in 24-month-old mice) after artery occlusion. This was not associated with rarefaction of similarly sized arterioles. Collateral remodeling was also reduced.
  
  
  CONCLUSIONS
  Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury.
authors: Department of Physiology, McAllister Heart Institute, University of North Carolina, Chapel Hill, 27599-7545, USA. jefaber@med.unc.edu
authors: James E
authors: JE
authors: Faber
authors: Hua
authors: H
authors: Zhang
authors: Roberta M
authors: RM
authors: Lassance-Soares
authors: Pranay
authors: P
authors: Prabhakar
authors: Amir H
authors: AH
authors: Najafi
authors: Mary Susan
authors: MS
authors: Burnett
authors: Stephen E
authors: SE
authors: Epstein
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