Abstract 14451: Role of Thrombospondin -1 in the Remodeling Induced by a Chronic Increase in Flow in Resistance Arteries
Background: Chronic increases in blood flow in resistance arteries induce outward vascular remodeling due to increased NO-dependent dilation and MMP activation. Although thrombospondin-1 (TSP-1) interacts with a variety of matrix proteins and cell-surface receptors, controversy remains about its vascular functions. We investigated the role of TSP-1 in high flow (HF)-mediated remodeling of resistance artery. Material and methods: Mesenteric arteries were ligated in vivo in order to generate high-flow arteries compared with normal flow (control) vessels located at distance on wild type (WT) and TSP-1 deleted mice (TSP-1 KO). Arteries were isolated 4 days to 1 week after ligature. Diameter and arteries reactivity were studied in vitro in an arteriograph. Genes implicated in inflammation and immune cells recruitment were determined in HF and NF arteries.
Results: Increases in diameter (from 221±9 to 280±9 µm, for a pressure of 75 mmHg) found between WT NF and WT HF arteries were not significant in TSP-1 KO arteries (from 296±17 to 303±14 µm). Dilatory (sodium nitroprusside) and contractile (Phenylephrine) tone, depending on the smooth muscle, were unaffected by the absence of TSP-1. We also demonstrated, after 4 days of ligature, an increase in CD68, Cox1, Cox2, Gp91phox, p47phox, p22phox, expression level between NF and HF WT arteries which was not observed in KO arteries. Furthermore, after 4 days of ligature, we observed a rise in neutrophils and lymphocytes number in response to chronic increase in blood flow in WT arteries, this rise was less important in the arteries of KO mice suggesting a role for TSP-1 in the recruitment of immune cells allowing the inflammatory response leading to remodeling.
Conclusion: The absence of TSP-1 induced a decrease in flow-induced remodeling with a reduction of the inflammatory response and of the endothelium-mediated dilation involved in HF remodeling. The deficiency in flow-induced remodeling was also associated with a reduction in the immune cells recruitment involved in the initiation of the remodeling.
- © 2012 by American Heart Association, Inc.