Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 24, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn050
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Blood flow-dependent arterial remodeling is facilitated by inflammation but directed by vascular tone
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: Erik N.T.P. Bakker, Dept. of Medical Physics, Academic Medical Center and Cardiovascular Research Institute Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands, Tel: +31 20 5665190 Fax: +31 20 6917233, Email: n.t.bakker{at}amc.uva.nl
Aim: Altered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodeling. We tested the hypothesis that inflammation facilitates the remodelling response, but that vascular tone determines its direction (inward or outward).
Methods: 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 remodeling was studied after two 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 remodeling, arteries were treated with the vasodilator amlodipine during organ culture.
Results: Vessels exposed to high blood flow dilated, whereas low flow induced constriction. After one 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 remodeling. Manipulation of vascular tone reversed inward remodeling in response to low blood flow.
Conclusion: Altered blood flow triggers an inflammatory response that facilitates remodeling. Vascular tone is a crucial determinant of the direction of the remodeling response.
Time for primary review: 30 days
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