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

• DOI: 10.1016/j.molmet.2023.101756
• Publication Date: 2023-06-20T12:47:41Z
• Authors: Xiaoling Cao; Vi Nguyen; Joseph Tsai; Chao Gao; Yan Tian; Yuping Zhang; Wayne Carver; Hippokratis Kiaris; Taixing Cui; Wenbin Tan
• Keywords: Cardiac Fibrosis

As the pandemic evolves, post-acute sequelae of CoV-2 (PASC) including cardiovascular manifestations have emerged as a new health threat. This study aims to whether Spike protein plus obesity can exacerbate PASC-related cardiomyopathy.A protein-pseudotyped (Spp) virus with proper surface tropism SARS-CoV-2 was developed for viral entry assay in vitro and administration into high fat diet (HFD)-fed mice. The systemic loads cardiac transcriptomes were analyzed at 2 24 h, 3, 6, weeks post introducing (wpi) Spp using RNA-seq or real time RT-PCR. Echocardiography used monitor functions.Low-density lipoprotein cholesterol enhanced uptake endothelial cells, macrophages, cardiomyocyte-like H9C2 cells. Selective adipose depositions observed HFD mice but not normal-chow-fed transcriptional signatures wpi showed suppression mitochondria respiratory chain genes ATP synthases nicotinamide adenine dinucleotide:ubiquinone oxidoreductase gene members, upregulation stress pathway-related crucial factors such nuclear factor-erythroid 2-related factor 1 signal transducer activator transcription 5A, increases expression glucose metabolism-associated genes. compared age-matched control mice, ejection fraction fractional shortening significantly decreased, while left ventricular end-systolic diameter volume elevated, fibrosis increased wpi.Our data demonstrated that could induce long-term metabolic cause myocardial contractile impairment obese providing mechanistic insights cardiomyopathy.