Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation
-
Published:2023-12-16
Issue:1
Volume:21
Page:
-
ISSN:1479-5876
-
Container-title:Journal of Translational Medicine
-
language:en
-
Short-container-title:J Transl Med
Author:
Dai Shiyu,Cao Ting,Shen Han,Zong Xuejing,Gu Wenyu,Li Hanghang,Wei Lei,Huang Haoyue,Yu Yunsheng,Chen Yihuan,Ye Wenxue,Hua Fei,Fan Hongyou,Shen Zhenya
Abstract
Abstract
Background
SARS-CoV-2, the pathogen of COVID-19, is a worldwide threat to human health and causes a long-term burden on the cardiovascular system. Individuals with pre-existing cardiovascular diseases are at higher risk for SARS-CoV-2 infection and tend to have a worse prognosis. However, the relevance and pathogenic mechanisms between COVID-19 and cardiovascular diseases are not yet completely comprehended.
Methods
Common differentially expressed genes (DEGs) were obtained in datasets of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2 and myocardial tissues from heart failure patients. Further GO and KEGG pathway analysis, protein–protein interaction (PPI) network construction, hub genes identification, immune microenvironment analysis, and drug candidate predication were performed. Then, an isoproterenol-stimulated myocardial hypertrophy cell model and a transverse aortic constriction-induced mouse heart failure model were employed to validate the expression of hub genes.
Results
A total of 315 up-regulated and 78 down-regulated common DEGs were identified. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive immune inflammation as the most prominent shared features of COVID-19 and cardiovascular diseases. Then, hub DEGs, as well as hub immune-related and mitochondria-related DEGs, were screened. Additionally, nine potential therapeutic agents for COVID-19-related cardiovascular diseases were proposed. Furthermore, the expression patterns of most of the hub genes related to cardiovascular diseases in the validation dataset along with cellular and mouse myocardial damage models, were consistent with the findings of bioinformatics analysis.
Conclusions
The study unveiled the molecular networks and signaling pathways connecting COVID-19 and cardiovascular diseases, which may provide novel targets for intervention of COVID-19-related cardiovascular diseases.
Funder
National Natural Science Foundation of China Jiangsu Cardiovascular Medicine Innovation Center Science Foundation of the First Affiliated Hospital of Soochow University
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference101 articles.
1. Chung MK, Zidar DA, Bristow MR, Cameron SJ, Chan T, Harding CV 3rd, Kwon DH, Singh T, Tilton JC, Tsai EJ, et al. COVID-19 and cardiovascular disease: from bench to bedside. Circ Res. 2021;128:1214–36. 2. Gyongyosi M, Alcaide P, Asselbergs FW, Brundel B, Camici GG, Martins PDC, Ferdinandy P, Fontana M, Girao H, Gnecchi M, et al. Long COVID and the cardiovascular system-elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: a joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial and Pericardial Diseases. Cardiovasc Res. 2023;119:336–56. 3. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21:133–46. 4. Alvarez-Garcia J, Lee S, Gupta A, Cagliostro M, Joshi AA, Rivas-Lasarte M, Contreras J, Mitter SS, LaRocca G, Tlachi P, et al. Prognostic impact of prior heart failure in patients hospitalized with COVID-19. J Am Coll Cardiol. 2020;76:2334–48. 5. Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, Banerjee A. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ. 2021;372: n693.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|