Abstract 13822: 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 increases NO-dependant dilation and MMP activation. Although thrombospondin-1 (TSP-1) interacts with matrix proteins and cell-surface receptors, controversy remains about its vascular functions. We investigate the role of TSP-1 in high flow (HF)-mediated remodeling of resistance arteries.
Material and Methods: Mesenteric arteries were ligated in vivo to generate HF arteries compared with normal flow (NF) vessels on wild type (WT) and TSP-1 deleted (KO) mice. Arteries were isolated from 4 days to 1 month after ligature. Arteries diameter and reactivity were studied in vitro in an arteriograph. Genes and proteins implicated in inflammation, remodeling, and immune cells recruitment were determined in HF and NF arteries.
Results: Increases in diameter found between WT NF and WT HF arteries were not significant in KO arteries. Contrary to KO arteries the diameter increase in WT arteries were correlated to an increase in wall thickness. Furthermore KO arteries were less responsive to Ach induced dilation than WT arteries.
After 4 days of ligature, we observed an increase in pro-inflammatory (CD68, Cox2, Gp91 phox, p47 phox, p22phox) gene expression between NF and HF WT arteries which was not observed in KO arteries. Moreover we also saw a rise in leukocytes number in response to chronic increase in blood flow in WT arteries, which was less important in KO arteries, suggesting a role of TSP-1 in the recruitment of immune cells allowing the inflammatory response leading to hypertrophic outward remodeling.
In bone marrow cells transfer experiments, we also demonstrated that circulating cells secreted TSP-1 and vascular cells secreted TSP-1 are implicated differently in artery flow-induced remodeling (wall hypertrophy and diameter).
Conclusion: The absence of TSP-1 leaded to a decrease in flow-induced dilation remodeling with a reduction of the inflammatory response and of the endothelium-mediated dilation involved in HF remodeling. The deficiency in remodeling was also associated with a decrease in the immune cells recruitment involved in the initiation of the remodeling.
Author Disclosures: C. Grenier: None. A. Caillon: None. L. Grimaud: None. A. Ayer: None. B. Toutain: None. V. Sauzeau: None. G. Loirand: None. O. Blanc-Brude: None. D. Henrion: None. L. Loufrani: None.
- © 2014 by American Heart Association, Inc.