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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiovascular Pharmacology and Drug Discovery
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1417701
This article is part of the Research Topic Novel Pharmacologic Therapeutics in Cardiovascular Diseases View all 3 articles

Identification and validation of CCL5 as a key gene in HIV infection and pulmonary arterial hypertension

Provisionally accepted
Mengyue Yang Mengyue Yang 1Wen Bi Wen Bi 2Zhijie Zhang Zhijie Zhang 1*
  • 1 Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China
  • 2 Department of Sports Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China

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

    Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH. Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB). Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina. Conclusion: This study revealed that CCL5 might be a common genetic feature of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.

    Keywords: HIV infection, PAH, DEGs, CCL5, molecular docking

    Received: 15 Apr 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Yang, Bi and Zhang. 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: Zhijie Zhang, Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.