Title

Roles of macrophages in flow-induced outward vascular remodeling

Document Type

Article

Abstract

Sustained hemodynamic stresses, especially sustained high blood flow, result in flow-induced outward vascular remodeling. Mechanisms that link hemodynamic stresses to vascular remodeling are not well understood. Inflammatory cells, known for their release of proteinases, including matrix metalloproteinases (MMPs), are emerging as key mediators for various tissue remodeling. Using a flow-augmented common carotid artery model in rats, we tested whether macrophages play critical roles in adaptive outward vascular remodeling in response to an increase in blood flow. Left common carotid artery ligation caused a sustained increase in blood flow with a gradual increase in luminal diameter in the right common carotid artery. Macrophages infiltrated into the vascular wall that peaked 3 days after flow augmentation. The time course of MMP-9 expression coincided with infiltration of macrophages. Macrophage depletion by liposome-encapsulated dichloromethylene diphosphonate significantly reduced flow-induced outward vascular remodeling, as indicated by the smaller luminal diameter of flow-augmented right common carotid artery in the clodronate-treated group compared with the phosphate-buffered saline-treated group (P<0.05). These data show critical roles of macrophages in flow-induced outward vascular remodeling. Inflammatory cell infiltration and their subsequent release of cytokines may be key processes for flow-induced outward vascular remodeling.

Medical Subject Headings

Animals; Carotid Artery, Common (enzymology, pathology); Carotid Stenosis (enzymology, pathology, physiopathology); Disease Models, Animal; Endothelium, Vascular (enzymology, pathology); Gelatinases (metabolism); Macrophages (enzymology, pathology); Male; Rats; Rats, Sprague-Dawley; Regional Blood Flow (physiology)

Publication Date

3-1-2009

Publication Title

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

E-ISSN

1559-7016

Volume

29

Issue

3

First Page

495

Last Page

503

PubMed ID

19002198

Digital Object Identifier (DOI)

10.1038/jcbfm.2008.136

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