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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiovascular Genetics and Systems Medicine
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1441123

miR-3529-3p/ABCA1 axis regulates smooth muscle cell homeostasis by enhancing inflammation via JAK2/STAT3 pathway

Provisionally accepted
Tingyu Wang Tingyu Wang *You Yu You Yu Yinglong Ding Yinglong Ding *Ziying Yang Ziying Yang *Shumin Jiang Shumin Jiang *Shan Liu Shan Liu *Faxiong Gao Faxiong Gao *Lianbo Shao Lianbo Shao *Zhenya Shen Zhenya Shen *
  • Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China

The final, formatted version of the article will be published soon.

    Thoracic Aortic Dissection (TAD) is a life-threatening disease without effective drug treatments. The disruption of Human Aortic Smooth Muscle Cells (HASMCs) homeostasis is one direct histopathologic alteration in TAD pathological process.Several miRNAs have been shown abnormally expressed in TAD and to regulate HASMCs homeostasis. Bulk miRNA sequencing was performed to explore the aberrantly expressed miRNA profile in TAD, and the result showed miR-3529 was elevated in TAD tissues and confirmed by qRT-PCR. Further experimental assay revealed miR-3529 upregulation induced HASMCs homeostasis disruption, accompanied by reducing contractile markers and increasing pro-inflammatory cytokines. Integrative transcriptomics and metabolomics analysis were used to uncover the functional roles of miR-3529 in regulating HASMCs homeostasis. The data showed that miR-3529 overexpression altered the metabolic profile of HASMCs, particularly lipid metabolism. ABCA1 was found to be a direct target of miR-3529, which was verified through a dual-luciferase reporter assay. Mechanistically, the miR-3529/ABCA1 axis disrupted HASMCs homeostasis and promoted inflammatory responses through the JAK2/STAT3 signaling pathway. These findings favor a role for miR-3529 as a novel target for TAD therapy.

    Keywords: Thoracic aortic dissection, Smooth Muscle Cell, Homeostasis, miR-3529-3p, ABCA1

    Received: 11 Jun 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Wang, Yu, Ding, Yang, Jiang, Liu, Gao, Shao and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Tingyu Wang, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Yinglong Ding, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Ziying Yang, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Shumin Jiang, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Shan Liu, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Faxiong Gao, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Lianbo Shao, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China
    Zhenya Shen, Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, China, Suzhou, Liaoning Province, China

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