Flow-dependent remodeling of small arteries in mice deficient for tissue-type transglutaminase: Possible compensation by macrophage-derived factor XIII

Erik N T P Bakker, Adrian Pistea, Jos A E Spaan, Titia Rolf, Carlie J. De Vries, Nico Van Rooijen, Eleonara Candi, Ed Vanbavel

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic changes in blood flow induce an adaptation of vascular caliber. Thus, arteries show inward remodeling after a reduction in blood flow. We hypothesized that this remodeling depends on the crosslinking enzyme tissue-type transglutaminase (tTG). Flow-dependent remodeling was studied in wild-type (WT) and tTG-null mice using a surgically imposed change in blood flow in small mesenteric arteries. WT mice showed inward remodeling after 2 days of low blood flow, which was absent in arteries from tTG-null mice. Yet, after continued low blood flow for 7 days, inward remodeling was similar in arteries from WT and tTG-null mice. Studying the alternative pathways of remodeling, we identified a relatively high expression of the plasma transglutaminase factor XIII in arteries of WT and tTG-null mice. In addition, vessels from both WT and tTG-null mice showed the presence of transglutaminase-specific crosslinks. An accumulation of adventitial monocytes/macrophages was found in vessels exposed to low blood flow in tTG-null mice. Because monocytes/macrophages may represent a source of factor XIII, tTG-null mice were treated with liposome-encapsulated clodronate. Elimination of monocytes/macrophages with liposome-encapsulated clodronate reduced both the expression of factor XIII and inward remodeling in tTG-null mice. In conclusion, tTG plays an important role in the inward remodeling of small arteries associated with decreased blood flow. Adventitial monocytes/macrophages are a source of factor XIII in tTG-null mice and contribute to an alternative, delayed mechanism of inward remodeling when tTG is absent.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalCirculation Research
Volume99
Issue number1
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Blood flow
  • Macrophages
  • Resistance arteries
  • Transglutaminase
  • Vascular remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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