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Cardiovascular Research Advance Access originally published online on February 24, 2008
Cardiovascular Research 2008 78(2):341-348; doi:10.1093/cvr/cvn050
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone

Erik N.T.P. Bakker1,*, Hanke L. Matlung1, Peter Bonta2, Carlie J. de Vries2, Nico van Rooijen3 and Ed VanBavel1

1 Department of Medical Physics, Academic Medical Center, Amsterdam, the Netherlands
2 Department of Medical Biochemistry, Academic Medical Center, Amsterdam, the Netherlands
3 Department of Molecular Cell Biology, Faculty of Medicine, Free University, Amsterdam, the Netherlands

* Corresponding author: Department of Medical Physics, Academic Medical Center and Cardiovascular Research Institute Amsterdam, Room L0-59, PO Box 22700, 1100 DE Amsterdam, the Netherlands Tel: +31 20 5665190; fax: +31 20 6917233. E-mail address: n.t.bakker{at}amc.uva.nl

Aims: 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).

Methods and 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.

Conclusion: Altered blood flow triggers an inflammatory response that facilitates remodelling. Vascular tone is a crucial determinant of the direction of the remodelling response.

KEYWORDS Arteries; Vasoconstriction/dilation; Remodelling; Blood flow; Macrophages

Time for primary review: 30 days


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