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

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

doi:10.1016/j.athplu.2022.10.001

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

Atheroscler Plus. 2022 Oct 19:50:57-64. doi: 10.1016/j.athplu.2022.10.001. eCollection 2022 Dec.

Authors

Zhonghua Wang^{1

2}, Guoliang Li¹, Mingpeng Li², Lu Hu², Zichen Hao², Qian Li¹, Chaofeng Sun¹

Affiliations

¹ Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Department of Cardiovascular Medicine, Affiliated to the First People's Hospital of Chenzhou of University of South China, Chenzhou No. 1 People's Hospital, The First Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, China.

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.

Keywords: Adventitial fibroblasts; Adventitial remodeling; Atherosclerosis; COL1A1, collagen Ⅰ; COL3A1, collagen Ⅲ; DMEM, Dulbecco's modified Eagle's medium; ECM, extracellular matrix; FAK, focal adhesion kinase; FBS, fetal bovine serum; MCP1, monocyte chemotactic protein-1; MMPs, matrix metalloproteinases; POSTN; POSTN, periostin; TGF-β1; TGF-β1, transforming growth factor-β1; qRT-PCR, quantitative real-time polymerase chain reaction; α-SMA, α-smooth muscle actin.