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一种源自 I 型胶原的基质细胞衍生因子可增加诱导血栓形成后小鼠主动脉血管壁重塑。

A collagen I derived matricryptin increases aorta vascular wall remodeling after induced thrombosis in mouse.

机构信息

Department of Structural and Functional Biology, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), São Paulo, Brazil.

出版信息

Thromb Res. 2022 Jan;209:59-68. doi: 10.1016/j.thromres.2021.11.021. Epub 2021 Dec 3.

DOI:10.1016/j.thromres.2021.11.021
PMID:34871983
Abstract

Matricryptins are collagen fragments proteolytically released from the extracellular matrix (ECM) with biological activity that can regulate several processes involved in ECM remodeling. Vessel wall matrix reorganization after lesion is important to the recovery of vascular function. This study aimed to analyze the effect of the peptide p1158/59 (Lindsey, 2015) on thrombosis, neointimal formation, and vascular remodeling of C57BL6 mice abdominal aorta. We used a FeCl induced vascular injury mice model and analyzed thrombus size, neointima formation, gelatinase activities in situ, re-endothelization, and collagen fibers organization on the arterial wall using polarization microscopy. As result, we observed that 2 days after injury the treatment with p1158/59 increased thrombus size and gelatinase activity, vascular lesion and it did not recover the endothelium loss induced by the chemical injury. We also observed that the peptide increased neointima growth and collagen birefringence, indicating collagen fibers reorganization. It also promoted increased re-endothelization and decreased activity of gelatinases 14 days after injury. Thus, we conclude that the peptide p1158/59 impaired the initial thrombosis recovery 2 days after injury but was able to induce vascular ECM remodeling after 14 days, improving vessel re-endothelization, collagen fibers deposition, and organization.

摘要

基质细胞衍生因子是细胞外基质(ECM)中经蛋白水解酶释放的胶原片段,具有生物活性,可调节 ECM 重塑过程中的多个过程。损伤后血管壁基质的重新组织对于血管功能的恢复很重要。本研究旨在分析肽 p1158/59(Lindsey,2015)对 C57BL6 小鼠腹主动脉血栓形成、新生内膜形成和血管重塑的影响。我们使用 FeCl3 诱导的血管损伤小鼠模型,并用偏光显微镜分析血栓大小、新生内膜形成、原位明胶酶活性、再内皮化和动脉壁胶原纤维组织。结果表明,损伤后 2 天,p1158/59 治疗组血栓增大和明胶酶活性增加,血管损伤,且不能恢复化学损伤引起的内皮丢失。我们还观察到,该肽增加了新生内膜生长和胶原双折射,表明胶原纤维的重组。它还促进了损伤后 14 天再内皮化和明胶酶活性的增加。因此,我们得出结论,该肽 p1158/59 在损伤后 2 天会损害初始血栓的恢复,但在 14 天后能够诱导血管 ECM 重塑,改善血管再内皮化、胶原纤维沉积和组织。

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