Thrombospondin-1 (TSP1) contributes to the development of vascular inflammation by regulating monocytic cell motility in mouse models of abdominal aortic aneurysm.
Thrombospondin-1 (TSP1) contributes to the development of vascular inflammation by regulating monocytic cell motility in mouse models of abdominal aortic aneurysm.
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DOI：
10.1161/circresaha.117.305262
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发表时间：
2015-07-03
影响因子：
20.1
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Liu Z;Morgan S;Ren J;Wang Q;Annis DS;Mosher DF;Zhang J;Sorenson CM;Sheibani N;Liu B
腹主动脉瘤（AAA）组织的组织学检查显示细胞外基质（ECM）破坏和炎性细胞浸润。先前对AAA小鼠模型的研究表明，抗炎策略可以有效地减弱动脉瘤形成。血小板反应蛋白-1（TSP 1）是一种基质细胞蛋白，通过调节细胞增殖、凋亡和粘附等生物学功能参与维持血管结构和稳态。TSP 1的表达水平与血管疾病状况相关。使用TSP 1缺陷（Thbs 1-/-）小鼠来检验TSP 1参与AAAs发病机制的假设。通过磷酸钙血管周围处理、猪弹性蛋白酶腔内灌注或血管紧张素II全身给药诱导小鼠实验性AAA。AAA的诱导增加了C57 BL/6或apoE−/−小鼠睾丸中TSP 1的表达。与Thbs 1 +/+小鼠相比，Thbs 1 −/−小鼠在AAA诱导下发生的主动脉扩张明显较小，这与巨噬细胞浸润减少有关。Thbs 1 −/−单核细胞在体外的粘附和迁移能力比野生型相应细胞降低。Thbs 1 +/+单核细胞的连续转移或骨髓重建挽救了Thbs 1 −/−小鼠的动脉瘤发展。TSP 1表达在调节单核细胞的迁移和粘附中起重要作用，有助于AAA发展过程中的血管炎症。
Histological examination of abdominal aortic aneurysm (AAA) tissues demonstrates extracellular matrix (ECM) destruction and infiltration of inflammatory cells. Previous work with mouse models of AAA has shown that anti-inflammatory strategies can effectively attenuate aneurysm formation. Thrombospondin-1 (TSP1) is a matricellular protein involved in the maintenance of vascular structure and homeostasis through the regulation of biological functions such as cell proliferation, apoptosis, and adhesion. Expression levels of TSP1 correlate with vascular disease conditions. To use TSP1 deficient (Thbs1−/−) mice to test the hypothesis that TSP1 contributes to pathogenesis of AAAs. Mouse experimental AAA was induced either through perivascular treatment with calcium phosphate, intraluminal perfusion with porcine elastase, or systemic administration of Angiotensin II. Induction of AAA increased TSP1 expression in aortas of C57BL/6 or apoE−/− mice. Compared to Thbs1+/+ mice, Thbs1−/− mice developed significantly smaller aortic expansion when subjected to AAA inductions, which was associated with diminished infiltration of macrophages. Thbs1−/− monocytic cells had reduced adhesion and migratory capacity in vitro compared to wildtype counterparts. Adoptive transfer of Thbs1+/+ monocytic cells or bone marrow reconstitution rescued aneurysm development in Thbs1−/− mice. TSP1 expression plays a significant role in regulation of migration and adhesion of mononuclear cells, contributing to vascular inflammation during AAA development.