Aging causes collateral rarefaction and increased severity of ischemic injury in multiple tissues

James E. Faber, Hua Zhang, Roberta M. Lassance-Soares, Pranay Prabhakar, Amir H. Najafi, Mary Susan Burnett, Stephen E. Epstein

Research output: Contribution to journalArticle

122 Scopus citations

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. Methods and 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. Conclusion-: Our findings demonstrate that aging causes rarefaction and insufficiency of the collateral circulation in multiple tissues, resulting in more severe ischemic tissue injury.

Original languageEnglish (US)
Pages (from-to)1748-1756
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • aging
  • angiogenesis
  • collateral circulation
  • ischemia
  • vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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