Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes
| العنوان: | Genes Encoding ACE2, TMPRSS2 and Related Proteins Mediating SARS-CoV-2 Viral Entry are Upregulated with Age in Human Cardiomyocytes |
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| المؤلفون: | Anthony P. Davenport, H. Llewelyn Roderick, Emma L. Robinson, Kanar Alkass, Janet J. Maguire, Olaf Bergmann |
| المساهمون: | Cardiologie, RS: Carim - H02 Cardiomyopathy, Maguire, Janet [0000-0002-9254-7040], Davenport, Anthony [0000-0002-2096-3117], Apollo - University of Cambridge Repository |
| المصدر: | Journal of Molecular and Cellular Cardiology, 147, 88-91. ELSEVIER SCI LTD Journal of Molecular and Cellular Cardiology |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, Cathepsin L, ACE, angiotensin I converting enzyme, Disease, 030204 cardiovascular system & hematology, BDKRB2, bradykinin receptor B2, ComputingMethodologies_ARTIFICIALINTELLIGENCE, Cathepsin B, Angiotensin, 0302 clinical medicine, Interferon, MAS1, MAS1 proto-oncogene G protein-coupled receptor, Medicine, TMPRSS11D, transmembrane protease serine 11D, Myocytes, Cardiac, TMPRSS2, transmembrane protease serine 2, Young adult, Furin, IFNAR1, interferon (alpha beta and omega) receptor 1, biology, Serine Endopeptidases, Interleukin, AGTR1, angiotensin II receptor type 1, Apelin, BDKRB1, bradykinin receptor B1, apelin, Interferon gamma receptor 1, TMPRSS11E, transmembrane protease serine 11E, Angiotensin-Converting Enzyme 2, Cardiology and Cardiovascular Medicine, Coronavirus Infections, medicine.drug, Angiotensins, InformationSystems_INFORMATIONSTORAGEANDRETRIEVAL, Pneumonia, Viral, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, RNA-sequencing, CTSB, cathepsin B, Virus Attachment, APLNR, apelin receptor, IRF1, interferon regulatory factor 1 (regulates transcription of interferons), Peptidyl-Dipeptidase A, Bradykinin, FURIN, furin (paired basic amino acid cleaving enzyme), TMPRSS2, Article, 03 medical and health sciences, Betacoronavirus, Downregulation and upregulation, Humans, ADAM17, ADAM metallopeptidase domain 17, IL6R, interleukin 6 receptor, Molecular Biology, Pandemics, Gene, ComputingMethodologies_COMPUTERGRAPHICS, SLC6A19, solute carrier family 6 (neutral amino acid transporter) member 19 (aka B0AT1), SARS-CoV-2, business.industry, Myocardium, human cardiomyocytes, IFNAR2, interferon (alpha beta and omega) receptor 2 (IFNAR1and 2 form chains for interferons alpha and beta), COVID-19, Virus Internalization, angiotensin, CTSL, cathepsin L, ComputingMethodologies_PATTERNRECOGNITION, 030104 developmental biology, Immunology, biology.protein, IFNGR1, Interferon gamma receptor 1, Human cardiomyocytes, ACE2, angiotensin I converting enzyme 2, business |
| الوصف: | Age is an independent risk factor for adverse outcome in patients following COVID-19 infection. We hypothesised that differential expression of genes encoding proteins proposed to be required for entry of SARS-Cov-2 in aged compared to younger cardiomyocytes might contribute to the susceptibility of older individuals to COVID-19-associated cardiovascular complications.We generated strand-specific RNA-sequencing libraries from RNA isolated from flow-sorted cardiomyocyte nuclei from left ventricular tissue. RNASeq data were compared between five young (19-25yr) and five older (63-78yr) Caucasian males who had not been on medication or exhibited evidence of cardiovascular disease post-mortem.Expression of relevant genes encoding ACE2, TMPRSS2, TMPRS11D, TMPRS11E, FURIN, CTSL, CTSB and B0AT1/SLC6A19 were upregulated in aged cardiomyocytes and the combined relative cardiomyocyte expression of these genes correlated positively with age. Genes encoding proteins in the RAAS and interferon/interleukin pathways were also upregulated such as ACE, AGTR1, MAS1 and IL6R.Our results highlight SARS-CoV-2 related genes that have higher expression in aged compared with young adult cardiomyocytes. These data may inform studies using selective enzyme inhibitors/antagonists, available as experimental compounds or clinically approved drugs e.g. remdesivir that has recently been rapidly accepted for compassionate use, to further understand the contribution of these pathways in human cardiomyocytes to disease outcome in COVID-19 patients. |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document; Print-Electronic |
| تدمد: | 0022-2828 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0f95f476673d68f64444c4caae84f8cf https://doi.org/10.1101/2020.07.07.191429 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0f95f476673d68f64444c4caae84f8cf |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 00222828 |
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