0259 : Neutrophil and thrombospondin-1 implications in flow-mediated remodeling of resistance arteries from mice

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• 作者：Tristan Champin¹ ; ^{tristan.champin@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Cé ; line Grenier¹ ; Olivier Blanc-Brude² ; Daniel Henrion¹ ; Laurent Loufrani¹
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：248
• 全文大小：48 K

文摘

On vascular endothelium, shear stress produces vasorelaxation and outward arterial remodeling. A chronic increase in blood flow induces arterial diameter expansion (normalizing shear stress), and is associated with a compensatory hypertrophy to normalize wall strain. This remodeling is due to Inflammation and nitric oxide (NO) production in resistance arteries. A large number of studies have demonstrated that Thrombospondin-1 (TSP1), a homotrimeric glycoprotein, can have an inhibitory action on the NO pathway and a positive effect on inflammation in vitro. Nevertheless, the role of TSP1 on remodeling is poorly understood. We hypothesized that TSP1 is able to participate in this outward arterial remodeling and hypertrophy by immune cells recruitment.

We investigated this remodeling in mesenteric resistance arteries of WT or TSP1-KO mice aged to 12-16 weeks were used. An IgG2a isotype control mAb 2A3 or Ly6G-specific mAb 1A8 are used for neutrophil depletion by in vivo administration. Ligation of mesenteric resistance arteries of WT/TSP1- KO and IgG2a/neutrophil-depleted mice allowed modifying blood flow in vivo, thus exposing arteries to low (LF), normal (NF), or high flow (HF). After 7 days, arteries were isolated for in vitro study. Phenylephrine-mediated contraction and Acetylcholine-mediated relaxation were stronger in HF than in NF vessels on WT and IgG2a control mice. Any difference between HF or NF in TSP1-KO and neutrophil-depleted mice were found. Furthermore, passive diameter analysis revealed a higher diameter in HF than NF in WT and IgG2a mice. These differences are lost in TSP1-KO and neutrophil-depleted mice. These results suggest that TSP1 are essential for remodeling in mesenteric arteries by promoting neutrophils recruitment.

The author hereby declares no conflict of interest