Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone.
OBJECTIVE
Altered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodelling. We tested the hypothesis that inflammation facilitates the remodelling response, but that vascular tone determines its direction (inward or outward).


RESULTS
Mouse mesenteric resistance arteries were ligated to create either increased blood flow or low blood flow in vivo. In vivo microscopy was used to determine changes in vascular tone. Structural remodelling was studied after 2 days, with or without macrophage depletion. In order to characterize the inflammatory response, immunostaining, confocal microscopy, and real-time PCR were used. To address the role of vascular tone in remodelling, arteries were treated with the vasodilator amlodipine during organ culture. Vessels exposed to high blood flow dilated, whereas low flow induced constriction. After 1 day, inflammatory markers showed a complex but remarkably similar increase in expression during high flow and low flow. Both high-flow and low-flow vessels showed an increase in the number of adventitial macrophages. Depletion of macrophages eliminated flow-induced remodelling. Manipulation of vascular tone reversed inward remodelling in response to low blood flow.


CONCLUSIONS
Altered blood flow triggers an inflammatory response that facilitates remodelling. Vascular tone is a crucial determinant of the direction of the remodelling response.
Bakker
Erik N T P
EN
Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands. n.t.bakker@amc.uva.nl
Matlung
Hanke L
HL
Bonta
Peter
P
de Vries
Carlie J
CJ
van Rooijen
Nico
N
Vanbavel
Ed
E
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008026:Ligation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D012039:Regional Blood Flow; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D018836:Inflammation Mediators; D014665:Vasodilator Agents; D017311:Amlodipine