Periostin contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Atherosclerosis plus Pub Date : 2022-12-01 DOI:10.1016/j.athplu.2022.10.001

Zhonghua Wang , Guoliang Li , Mingpeng Li , Lu Hu , Zichen Hao , Qian Li , Chaofeng Sun

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引用次数: 1

Abstract

Background and aims

Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis.

Methods

An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts.

Results

POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-β1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src.

Conclusions

Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

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骨膜蛋白通过激活外膜成纤维细胞参与动脉粥样硬化的外膜重塑

背景和目的外膜重构是动脉粥样硬化的一个重要病理过程，但与外膜重构相关的线索还远未完全了解。骨膜蛋白(POSTN)是一种基质细胞蛋白，已被证明在心血管疾病中具有多种作用。本研究的目的是探讨POSTN在动脉粥样硬化期间内皮重塑中的功能。方法采用ApoE-/-小鼠高脂高胆固醇饮食，建立小鼠动脉粥样硬化模型。采用免疫组化染色法检测小鼠动脉粥样硬化血管标本外膜中POSTN的表达。通过细胞收缩性和活化标志物α-平滑肌肌动蛋白(α-SMA)在过表达POSTN的外层成纤维细胞中的表达评估，评估POSTN在调节外层成纤维细胞活化中的作用。此外，我们采用定量实时聚合酶链反应(qRT-PCR)和Western blotting检测促炎趋化因子转化生长因子-β1 (TGF-β1)和单核细胞趋化蛋白1 (MCP1)以及一些细胞外基质(ECM)相关蛋白在过表达postn的上皮成纤维细胞中的表达。最后，我们在外层成纤维细胞中检测到POSTN过表达的整合素相关信号通路。结果在小鼠动脉粥样硬化模型中，spostn在动脉粥样硬化主动脉外膜中高表达，促进外膜成纤维细胞的活化和收缩。同时，POSTN还诱导外膜成纤维细胞表达TGF-β1、单核细胞趋化蛋白-1 (MCP1)和ecm相关蛋白，激活局灶黏附激酶(FAK)和Src的磷酸化。结论动脉粥样硬化过程中，动脉粥样硬化外膜中POSTN升高，并通过激活外膜成纤维细胞参与动脉粥样硬化外膜重构。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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