Single-Cell Transcriptome Analysis Decipher New Potential Regulation Mechanism of ACE2 and NPs Signaling Among Heart Failure Patients Infected With SARS-CoV-2

Frontiers in Cardiovascular Medicine

Xiaojiang Xu¹  Xiaojuan Fan²  Hong Li³  Yingjie Chen⁴  Dachun Xu⁵  Yanhua Xu⁷  Mengqiu Ma⁷  Yang Su⁷  Min Chai⁸  Xingdong Hu⁹  Maojun Zhao^1,11  Sang-Bing Ong^1,14 

[1] Biophysics, University of Mississippi Medical Center, Jackson, MS, United States;Disease Laboratory, The National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States;;0Immunity, Inflammation &1Key Laboratory of Environment and Genes Related to Diseases, Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;;2Department of Physiology &Centre for Cardiovascular Genomics and Medicine (CCGM), Lui Che Woo Institute of Innovative Medicine, Chinese University of Hong Kong (CUHK), Hong Kong, China;Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China;Department of Critical Care Medicine, Ezhou Central Hospital, Ezhou, China;Department of Critical Care Medicine, The Third people's Hospital of Guizhou Province, Guiyang, China;Department of Medicine and Therapeutics, Faculty of Medicine, Chinese University of Hong Kong (CUHK), Hong Kong, China;Emergency Department, The First People's Hospital of Guiyang, Guiyang, China;Hong Kong Hub of Paediatric Excellence (HK HOPE), Hong Kong Children's Hospital (HKCH), Hong Kong, China;Institute for Translational Medicine, Xiamen Cardiovascular Hospital, Xiamen University, Xiamen, China;Kunming Institute of Zoology–The Chinese University of Hong Kong (KIZ-CUHK) Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;

关键词: COVID-19;    SARS-CoV-2;    heart failure;    angiotensin converting enzyme 2;    single-cell RNA sequencing;   

DOI  :  10.3389/fcvm.2021.628885

来源: DOAJ

【 摘 要 】

Aims: COVID-19 patients with comorbidities such as hypertension or heart failure (HF) are associated with poor clinical outcomes. The cellular distribution of Angiotensin-converting enzyme 2 (ACE2), the critical enzyme for SARS-CoV-2 infection, in the human heart is unknown. We explore the underlying mechanism that leads to increased susceptibility to SARS-CoV-2 in patients with cardiovascular diseases and patients of cardiac dysfunction have increased risk of multi-organ injury compared with patients of normal cardiac function.Methods and Results: We analyzed single-cell RNA sequencing (scRNA-seq) data in both normal and failing hearts. The results demonstrated that ACE2 is present in cardiomyocytes (CMs) and non-CMs, while the number of ACE2-postive (ACE2+) CMs and ACE2 gene expression in these CMs are significantly increased in the failing hearts. Interestingly, both brain natriuretic peptides (BNP) and atrial natriuretic peptide (ANP) are significantly up-regulated in the ACE2+ CMs, which is consistent with other studies that ACE2, ANP, and BNP increased in HF patients. We found that genes related to virus entry, virus replication and suppression of interferon-gamma signaling are all up-regulated in failing CMs, and the increase was significantly higher in ACE2+ CMs, suggesting that these CMs may be more vulnerable to virus infection. As the level of expression of both ACE2 and BNP in CMs were up-regulated, we further performed retrospective analysis of the plasma BNP levels and clinical outcomes of 91 COVID-19 patients from a single-center. Patients with higher plasma BNP were associated with significantly higher mortality and expression levels of inflammatory and infective markers.Conclusion: In the failing heart, the upregulation of ACE2 and virus infection associated genes could potentially facilitate SARS-CoV-2 virus entry and replication in these vulnerable cardiomyocyte subsets. COVID-19 patients with higher plasma BNP levels had poorer clinical outcomes. These observations may allude to a potential regulatory association between ACE2 and BNP in mediating myocarditis associated with COVID-19.

【 授权许可】

Unknown