{"doi":"10.1101/2023.01.05.522853","title":"The SARS-CoV-2 Spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice","abstract":"Background: As the pandemic evolves, post-acute sequelae of CoV-2 (PACS) including cardiovascular manifestations have emerged as a new health threat. This study aims to study whether the Spike protein plus obesity can exacerbate PACS-related cardiomyopathy. Methods: and administration into high fat diet (HFD)-fed mice. The systemic viral loads and cardiac transcriptomes were analyzed at 2 and 24 hrs, 3, 6, and 24 weeks post introducing (wpi) Spp using RNA-seq or real time RT-PCR. Echocardiography was used to monitor cardiac functions. Results: Low-density lipoprotein cholesterol enhanced viral uptake in endothelial cells, macrophages, and cardiomyocyte-like H9C2 cells. Selective cardiac and adipose viral depositions were observed in HFD mice but not in normal-chow-fed mice. The cardiac transcriptional signatures in HFD mice at 3, 6, and 24 wpi showed systemic suppression of mitochondria respiratory chain genes including ATP synthases and nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation of stress pathway-related crucial factors such as nuclear factor-erythroid 2-related factor 1 and signal transducer and activator of transcription 5A, and increases in expression of glucose metabolism-associated genes. As compared with the age-matched HFD control mice, cardiac ejection fraction and fractional shortening were significantly decreased, while left ventricular end-systolic diameter and volume were significantly elevated, and cardiac fibrosis was increased in HFD mice at 24 wpi. Conclusion: Our data demonstrated that the Spike protein could induce long-term transcriptional suppression of mitochondria metabolic genes and cause cardiac fibrosis and myocardial contractile impairment, providing mechanistic insights to PACS-related cardiomyopathy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390889,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":682368,"name":"Vi Nguyen","orcid":"0000-0002-0688-0286","position":1,"is_corresponding":false},{"id":479415,"name":"Joseph C. Tsai","orcid":"0000-0002-0727-2020","position":2,"is_corresponding":false},{"id":292909,"name":"Chao Gao","orcid":"0000-0003-3489-3989","position":3,"is_corresponding":false},{"id":682367,"name":"Yan Tian","orcid":"0000-0001-5643-5765","position":4,"is_corresponding":false},{"id":355721,"name":"Yuping Zhang","orcid":"0000-0002-8600-9879","position":5,"is_corresponding":false},{"id":682370,"name":"Wayne Carver","orcid":"0000-0002-7699-6241","position":6,"is_corresponding":false},{"id":586766,"name":"Hippokratis Kiaris","orcid":"0000-0002-8999-8289","position":7,"is_corresponding":false},{"id":263770,"name":"Taixing Cui","orcid":"0000-0002-9528-7299","position":8,"is_corresponding":false},{"id":682371,"name":"Wenbin Tan","orcid":"0000-0002-2334-8988","position":9,"is_corresponding":false},{"id":682366,"name":"Xiaoling Cao","orcid":"0000-0003-4993-8385","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T01:18:42.653719Z","pmid":"36656778","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}