Flow‐induced remodeling: interplay of local inflammation and vascular tone

Abstract

We hypothesize that small artery remodeling is facilitated by inflammation but that smooth muscle cell tone sets its inward or outward direction.MethodsMouse mesenteric arcade arteries were ligated, resulting in low flow and high flow vessels. Immediate effects on tone were determined by in vivo microscopy. Structural remodeling was quantified after two days.ResultsVessels exposed to high blood flow dilated, followed by outward remodeling. Low flow vessels constricted, followed by inward remodeling. Macrophage numbers increased 5‐fold in both groups, and remodeling was absent after macrophages depletion. Yet, the pattern of pro‐ and anti‐inflammatory cytokine expression was similar in high and low flow vessels. Low flow vessels under subsequent full dilation showed increased outward remodeling, as tested by a sequence of 1 day in vivo and 1 day in vitro study in a cannulation setup (13 ± 3% in inflamed arteries versus 6 ± 1% in control, n=5, p<0.05).ConclusionAltered blood flow is associated with an inflammatory response that facilitates remodeling; the direction is determined by vascular tone. Supported by the Netherlands Heart Foundation (NHS 2001T038).