Flow-dependent remodeling of small arteries in mice deficient for tissue-type transglutaminase: possible compensation by macrophage-derived factor XIII.
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.
Bakker
Erik N T P
EN
Department of Medical Physics, Academic Medical Center and Cardiovascular Research Institute Amsterdam, Amsterdam, The Netherlands. n.t.bakker@amc.uva.nl
Pistea
Adrian
A
Spaan
Jos A E
JA
Rolf
Titia
T
de Vries
Carlie J
CJ
van Rooijen
Nico
N
Candi
Eleonara
E
VanBavel
Ed
E
D000222:Adaptation, Physiological; D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D005176:Factor XIII / Q000037:antagonists & inhibitors / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000172:deficiency*; D066298:In Vitro Techniques; D008081:Liposomes; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000172:deficiency*
D008081:Liposomes; D004002:Clodronic Acid; D005176:Factor XIII; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins