{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:09:37Z","timestamp":1789614577101,"version":"build-2803163510"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002418","name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College","doi-asserted-by":"publisher","award":["2016-I2M-1-016"],"award-info":[{"award-number":["2016-I2M-1-016"]}],"id":[{"id":"10.13039\/501100002418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002418","name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College","doi-asserted-by":"publisher","award":["2019-I2M-1-001"],"award-info":[{"award-number":["2019-I2M-1-001"]}],"id":[{"id":"10.13039\/501100002418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002418","name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College","doi-asserted-by":"publisher","award":["2016-I2M-2-006"],"award-info":[{"award-number":["2016-I2M-2-006"]}],"id":[{"id":"10.13039\/501100002418","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Mega projects of China for Major Infectious Diseases","award":["2017ZX10304402"],"award-info":[{"award-number":["2017ZX10304402"]}]},{"name":"National Key Research and Development Project of China","award":["2016YFD0500304"],"award-info":[{"award-number":["2016YFD0500304"]}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["DK039308"],"award-info":[{"award-number":["DK039308"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J. of Cardiovasc. Trans. Res."],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis.<\/jats:p>","DOI":"10.1007\/s12265-021-10147-3","type":"journal-article","created":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T07:16:29Z","timestamp":1641021389000},"page":"38-48","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice"],"prefix":"10.1007","volume":"15","author":[{"given":"Xiaoliang","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huadong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjun","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangning","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhe","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A.","family":"Jose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6943-004X","authenticated-orcid":false,"given":"Zhiwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"10147_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet, 395, 497\u2013506. https:\/\/doi.org\/10.1016\/S0140-6736(20)30183-5.","journal-title":"Lancet"},{"key":"10147_CR2","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1001\/jama.2020.2648","volume":"323","author":"Z Wu","year":"2020","unstructured":"Wu, Z., & McGoogan, J. M. (2020). Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA, 323, 1239\u20131242. https:\/\/doi.org\/10.1001\/jama.2020.2648.","journal-title":"JAMA"},{"key":"10147_CR3","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1080\/22221751.2020.1729069","volume":"9","author":"X Tian","year":"2020","unstructured":"Tian, X., Li, C., Huang, A., Xia, S., Lu, S., Shi, Z., Lu, L., Jiang, S., Yang, Z., Wu, Y., et al. (2020). Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infect, 9, 382\u2013385. https:\/\/doi.org\/10.1080\/22221751.2020.1729069.","journal-title":"Emerg Microbes Infect"},{"key":"10147_CR4","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou, P., Yang, X. L., Wang, X. G., Hu, B., Zhang, L., Zhang, W., Si, H. R., Zhu, Y., Li, B., & Huang, C. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579, 270\u2013273. https:\/\/doi.org\/10.1038\/s41586-020-2012-7.","journal-title":"Nature"},{"key":"10147_CR5","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.bbrc.2020.02.071","volume":"525","author":"Y Chen","year":"2020","unstructured":"Chen, Y., Guo, Y., Pan, Y., & Zhao, Z. J. (2020). Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun, 525, 135\u2013140. https:\/\/doi.org\/10.1016\/j.bbrc.2020.02.071.","journal-title":"Biochem Biophys Res Commun"},{"key":"10147_CR6","doi-asserted-by":"publisher","first-page":"e026777","DOI":"10.1136\/bmjopen-2018-026777","volume":"9","author":"LJ Smyth","year":"2019","unstructured":"Smyth, L. J., Canadas-Garre, M., Cappa, R. C., Maxwell, A. P., & McKnight, A. J. (2019). Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: A systematic review and meta-analysis. BMJ Open, 9, e026777. https:\/\/doi.org\/10.1136\/bmjopen-2018-026777.","journal-title":"BMJ Open"},{"key":"10147_CR7","doi-asserted-by":"publisher","first-page":"C82","DOI":"10.1152\/ajpcell.00287.2006","volume":"292","author":"PK Mehta","year":"2007","unstructured":"Mehta, P. K., & Griendling, K. K. (2007). Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol, 292, C82\u2013C97. https:\/\/doi.org\/10.1152\/ajpcell.00287.2006.","journal-title":"Am J Physiol Cell Physiol"},{"key":"10147_CR8","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1152\/physrev.00023.2016","volume":"98","author":"RAS Santos","year":"2018","unstructured":"Santos, R. A. S., Sampaio, W. O., Alzamora, A. C., Motta-Santos, D., Alenina, N., Bader, M., & Campagnole-Santos, M. J. (2018). The ACE2\/Angiotensin-(1-7)\/MAS axis of the renin-angiotensin system: Focus on angiotensin-(1-7). Physiol Rev, 98, 505\u2013553. https:\/\/doi.org\/10.1152\/physrev.00023.2016.","journal-title":"Physiol Rev"},{"key":"10147_CR9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/ajh\/hpu086","volume":"28","author":"M Furuhashi","year":"2015","unstructured":"Furuhashi, M., Moniwa, N., Mita, T., Fuseya, T., Ishimura, S., Ohno, K., Shibata, S., Tanaka, M., Watanabe, Y., Akasaka, H., et al. (2015). Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker. Am J Hypertens, 28, 15\u201321. https:\/\/doi.org\/10.1093\/ajh\/hpu086.","journal-title":"Am J Hypertens"},{"key":"10147_CR10","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.yjmcc.2016.05.012","volume":"97","author":"X Wang","year":"2016","unstructured":"Wang, X., Ye, Y., Gong, H., Wu, J., Yuan, J., Wang, S., Yin, P., Ding, Z., Kang, L., Jiang, Q., et al. (2016). The effects of different angiotensin II type 1 receptor b lockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang (1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. J Mol Cell Cardiol, 97, 180\u2013190. https:\/\/doi.org\/10.1016\/j.yjmcc.2016.05.012.","journal-title":"J Mol Cell Cardiol"},{"key":"10147_CR11","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1161\/01.HYP.0000124667.34652.1a","volume":"43","author":"Y Ishiyama","year":"2004","unstructured":"Ishiyama, Y., Gallagher, P. E., Averill, D. B., Tallant, E. A., Brosnihan, K. B., & Ferrario, C. M. (2004). Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension, 43, 970\u2013976. https:\/\/doi.org\/10.1161\/01.HYP.0000124667.34652.1a.","journal-title":"Hypertension"},{"key":"10147_CR12","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1002\/ddr.21656","volume":"81","author":"D Gurwitz","year":"2020","unstructured":"Gurwitz, D. (2020). Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res, 81, 537\u2013540. https:\/\/doi.org\/10.1002\/ddr.21656.","journal-title":"Drug Dev Res"},{"key":"10147_CR13","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1161\/HYPERTENSIONAHA.120.15622","volume":"76","author":"F Zhou","year":"2020","unstructured":"Zhou, F., Liu, Y. M., Xie, J., Li, H., Lei, F., Yang, H., Qin, J. J., Cai, J., Zhang, X. J., Wu, B., et al. (2020). Comparative impacts of ACE inhibitors versus angiotensin II receptor blockers on the risk of COVID-19 mortality. Hypertension, 76, e15\u2013e17. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.15622.","journal-title":"Hypertension"},{"key":"10147_CR14","doi-asserted-by":"publisher","unstructured":"Hippisley-Cox J, Young D, Coupland C, Channon KM, Tan PS, Harrison DA, Rowan K, Aveyard P, Pavord ID, Watkinson PJ (2020). Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people. Heart. 317-393. https:\/\/doi.org\/10.1136\/heartjnl-2020-317393","DOI":"10.1136\/heartjnl-2020-317393"},{"key":"10147_CR15","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.jmii.2020.04.015","volume":"53","author":"CA Devaux","year":"2020","unstructured":"Devaux, C. A., Rolain, J. M., & Raoult, D. (2020). ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect, 53, 425\u2013435. https:\/\/doi.org\/10.1016\/j.jmii.2020.04.015.","journal-title":"J Microbiol Immunol Infect"},{"key":"10147_CR16","doi-asserted-by":"publisher","first-page":"e21","DOI":"10.1016\/S2213-2600(20)30116-8","volume":"8","author":"L Fang","year":"2020","unstructured":"Fang, L., Karakiulakis, G., & Roth, M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med, 8, e21. https:\/\/doi.org\/10.1016\/S2213-2600(20)30116-8.","journal-title":"Lancet Respir Med"},{"key":"10147_CR17","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1161\/CIRCULATIONAHA.120.047049","volume":"142","author":"K Wang","year":"2020","unstructured":"Wang, K., Gheblawi, M., & Oudit, G. Y. (2020). Angiotensin converting enzyme 2: A double-edged sword. Circulation, 142, 426\u2013428. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.120.047049.","journal-title":"Circulation"},{"key":"10147_CR18","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/s41586-020-2312-y","volume":"583","author":"L Bao","year":"2020","unstructured":"Bao, L., Deng, W., Huang, B., Gao, H., Liu, J., Ren, L., Wei, Q., Yu, P., Xu, Y., Qi, F., et al. (2020). The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature, 583, 830\u2013833. https:\/\/doi.org\/10.1038\/s41586-020-2312-y.","journal-title":"Nature"},{"key":"10147_CR19","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/s41586-020-2708-8","volume":"586","author":"KH Dinnon","year":"2020","unstructured":"Dinnon, K. H., Leist, S. R., Schafer, A., Edwards, C. E., Martinez, D. R., Montgomery, S. A., West, A., Yount, B. L., Hou, Y. J., Adams, L. E., et al. (2020). A mouse-adaptedSARS-CoV-2 model for the evaluation of COVID-19 medical countermeasures. Nature, 586, 560\u2013566. https:\/\/doi.org\/10.1038\/s41586-020-2708-8.","journal-title":"Nature"},{"key":"10147_CR20","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1161\/HYPERTENSIONAHA.120.15324","volume":"76","author":"G Iaccarino","year":"2020","unstructured":"Iaccarino, G., Grassi, G., Borghi, C., Ferri, C., Salvetti, M., Volpe, M., & SARS-RAS Investigators. (2020). Age and multimorbidity predict death among COVID-19 patients: Results of the SARS-RAS study of the Italian Society of Hypertension. Hypertension, 76, 366\u2013372. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.15324.","journal-title":"Hypertension"},{"key":"10147_CR21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40246-020-00272-6","volume":"14","author":"C Lutz","year":"2020","unstructured":"Lutz, C., Maher, L., Lee, C., & Kang, W. (2020). COVID-19 preclinical models: Human angiotensin-converting enzyme 2 transgenic mice. Hum Genomics, 14, 20. https:\/\/doi.org\/10.1186\/s40246-020-00272-6.","journal-title":"Hum Genomics"},{"key":"10147_CR22","first-page":"450","volume":"57","author":"XH Yang","year":"2007","unstructured":"Yang, X. H., Deng, W., Tong, Z., Liu, Y. X., Zhang, L. F., Zhu, H., Gao, H., Huang, L., Liu, Y. L., Ma, C. M., et al. (2007). Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med, 57, 450\u2013459.","journal-title":"Comp Med"},{"key":"10147_CR23","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.cell.2020.05.025","volume":"182","author":"Y Cao","year":"2020","unstructured":"Cao, Y., Su, B., Guo, X., Sun, W., Deng, Y., Bao, L., Zhu, Q., Zhang, X., Zheng, Y., Geng, C., et al. (2020). Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients' B cells. Cell, 182, 73\u201384. https:\/\/doi.org\/10.1016\/j.cell.2020.05.025.","journal-title":"Cell"},{"key":"10147_CR24","doi-asserted-by":"publisher","first-page":"m1091","DOI":"10.1136\/bmj.m1091","volume":"368","author":"T Chen","year":"2019","unstructured":"Chen, T., Wu, D., Chen, H., Yan, W., Yang, D., Chen, G., Ma, K., Xu, D., Yu, H., Wang, H., et al. (2019). Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ, 368, m1091. https:\/\/doi.org\/10.1136\/bmj.m1091.","journal-title":"BMJ"},{"key":"10147_CR25","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","volume":"382","author":"WJ Guan","year":"2019","unstructured":"Guan, W. J., Ni, Z. Y., Hu, Y., Liang, W. H., Ou, C. Q., He, J. X., Liu, L., Shan, H., Lei, C. L., Hui, D. S. C., et al. (2019). China Medical Treatment Expert Group. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med, 382, 1708\u20131720. https:\/\/doi.org\/10.1056\/NEJMoa2002032.","journal-title":"N Engl J Med"},{"key":"10147_CR26","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1007\/s11427-020-1643-8","volume":"63","author":"Y Liu","year":"2020","unstructured":"Liu, Y., Yang, Y., Zhang, C., Huang, F., Wang, F., Yuan, J., Wang, Z., Li, J., Li, J., Feng, C., et al. (2020). Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci, 63, 364\u2013374. https:\/\/doi.org\/10.1007\/s11427-020-1643-8.","journal-title":"Sci China Life Sci"},{"key":"10147_CR27","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.cell.2020.04.035","volume":"181","author":"CGK Ziegler","year":"2020","unstructured":"Ziegler, C. G. K., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., Cao, Y., Yousif, A. S., Bals, J., Hauser, B. M., et al. (2020). SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell, 181, 1016\u20131035. https:\/\/doi.org\/10.1016\/j.cell.2020.04.035.","journal-title":"Cell"},{"key":"10147_CR28","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1038\/nrclinonc.2010.9-c1","volume":"7","author":"AJ Ferreri","year":"2010","unstructured":"Ferreri, A. J., Illerhaus, G., Zucca, E., & Cavalli, F. (2010). Flows and flaws in primary central nervous system lymphoma. Nat Rev Clin Oncol, 7, 1038\u20131042. https:\/\/doi.org\/10.1038\/nrclinonc.2010.9-c1.","journal-title":"Nat Rev Clin Oncol"},{"key":"10147_CR29","doi-asserted-by":"publisher","first-page":"3594","DOI":"10.1038\/ncomms4594","volume":"5","author":"Z Zou","year":"2014","unstructured":"Zou, Z., Yan, Y., Shu, Y., Gao, R., Sun, Y., Li, X., Ju, X., Liang, Z., Liu, Q., Zhao, Y., et al. (2014). Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun, 5, 3594. https:\/\/doi.org\/10.1038\/ncomms4594.","journal-title":"Nat Commun"},{"key":"10147_CR30","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1016\/S2213-2600(20)30354-4","volume":"8","author":"E Pujadas","year":"2020","unstructured":"Pujadas, E., Chaudhry, F., McBride, R., Richter, F., Zhao, S., Wajnberg, A., Nadkarni, G., Glicksberg, B. S., Houldsworth, J., & Cordon-Cardo, C. (2020). SARS-CoV-2 viral load predicts COVID-19 mortality. Lancet Respir Med, 8, e70. https:\/\/doi.org\/10.1016\/S2213-2600(20)30354-4.","journal-title":"Lancet Respir Med"},{"key":"10147_CR31","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1080\/22221751.2020.1746200","volume":"9","author":"J Meng","year":"2020","unstructured":"Meng, J., Xiao, G., Zhang, J., He, X., Ou, M., Bi, J., Yang, R., Di, W., Wang, Z., Li, Z., et al. (2020). Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect, 9, 757\u2013760. https:\/\/doi.org\/10.1080\/22221751.2020.1746200.","journal-title":"Emerg Microbes Infect"},{"key":"10147_CR32","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1056\/NEJMoa2008975","volume":"382","author":"HR Reynolds","year":"2020","unstructured":"Reynolds, H. R., Adhikari, S., Pulgarin, C., Troxel, A. B., Iturrate, E., Johnson, S. B., Hausvater, A., Newman, J. D., Berger, J. S., Bangalore, S., et al. (2020). Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19. N Engl J Med, 382, 2441\u20132448. https:\/\/doi.org\/10.1056\/NEJMoa2008975.","journal-title":"N Engl J Med"},{"key":"10147_CR33","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1056\/NEJMoa2006923","volume":"382","author":"G Mancia","year":"2020","unstructured":"Mancia, G., Rea, F., Ludergnani, M., Apolone, G., & Corrao, G. (2020). Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med, 382, 2431\u20132440. https:\/\/doi.org\/10.1056\/NEJMoa2006923.","journal-title":"N Engl J Med"},{"key":"10147_CR34","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.kint.2020.03.005","volume":"97","author":"Y Cheng","year":"2020","unstructured":"Cheng, Y., Luo, R., Wang, K., Zhang, M., Wang, Z., Dong, L., Li, J., Yao, Y., Ge, S., & Xu, G. (2020). Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int, 97, 829\u2013838. https:\/\/doi.org\/10.1016\/j.kint.2020.03.005.","journal-title":"Kidney Int"},{"key":"10147_CR35","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1016\/S2213-2600(20)30229-0","volume":"8","author":"C Ronco","year":"2020","unstructured":"Ronco, C., Reis, T., & Husain-Syed, F. (2020). Management of acute kidney injury in patients with COVID-19. Lancet Respir Med, 8, 738\u2013742. https:\/\/doi.org\/10.1016\/S2213-2600(20)30229-0.","journal-title":"Lancet Respir Med"},{"key":"10147_CR36","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.jmii.2020.04.015","volume":"53","author":"CA Devaux","year":"2020","unstructured":"Devaux, C. A., Rolain, J. M., & Raoult, D. (2020). ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect., 53, 425\u2013435. https:\/\/doi.org\/10.1016\/j.jmii.2020.04.015.","journal-title":"J Microbiol Immunol Infect."},{"key":"10147_CR37","doi-asserted-by":"publisher","first-page":"10970","DOI":"10.1073\/pnas.2005615117","volume":"117","author":"X Xu","year":"2020","unstructured":"Xu, X., Han, M., Li, T., Sun, W., Wang, D., Fu, B., Zhou, Y., Zheng, X., Yang, Y., Li, X., et al. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A, 117, 10970\u201310975. https:\/\/doi.org\/10.1073\/pnas.2005615117.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10147_CR38","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1002\/art.41285","volume":"272","author":"LA Henderson","year":"2020","unstructured":"Henderson, L. A., Canna, S. W., Schulert, G. S., Volpi, S., Lee, P. Y., Kernan, K. F., Caricchio, R., Mahmud, S., Hazen, M. M., Halyabar, O., et al. (2020). On the alert for cytokine storm: Immunopathology in COVID-19. Arthritis Rheumatol, 272, 1059\u20131063. https:\/\/doi.org\/10.1002\/art.41285.","journal-title":"Arthritis Rheumatol"},{"key":"10147_CR39","doi-asserted-by":"publisher","unstructured":"Chaudhary R, Garg J, Houghton DE, Murad MH, Kondur A, Chaudhary R, Wysokinski WE, McBane RD 2nd Thrombo-inflammatory biomarkers in COVID-19: Systematic review and meta-analysis of 17,052 patients. Mayo Clin Proc Innov Qual Outcomes. 2021. https:\/\/doi.org\/10.1016\/j.mayocpiqo.2021.01.009. Online ahead of print.","DOI":"10.1016\/j.mayocpiqo.2021.01.009"},{"key":"10147_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1001\/jamacardio.2020","volume":"5","author":"RM Inciardi","year":"2020","unstructured":"Inciardi, R. M., Lupi, L., Zaccone, G., Italia, L., Raffo, M., Tomasoni, D., Cani, D. S., Cerini, M., Farina, D., Gavazzi, E., et al. (2020). Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiol, 5, 1\u20136. https:\/\/doi.org\/10.1001\/jamacardio.2020.","journal-title":"JAMA Cardiol"},{"key":"10147_CR41","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.pcad.2020.03.001","volume":"63","author":"G Lippi","year":"2020","unstructured":"Lippi, G., Lavie, C. J., & Sanchis-Gomar, F. (2020). Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis, 63, 390\u2013391. https:\/\/doi.org\/10.1016\/j.pcad.2020.03.001.","journal-title":"Prog Cardiovasc Dis"},{"key":"10147_CR42","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/nrcardio.2017.48","volume":"14","author":"D Westermann","year":"2017","unstructured":"Westermann, D., Neumann, J. T., Sorensen, N. A., & Collinson, P. O. (2017). High-sensitivity assays for troponin in patients with cardiac disease. Nat Rev Cardiol, 14, 472\u2013483. https:\/\/doi.org\/10.1038\/nrcardio.2017.48.","journal-title":"Nat Rev Cardiol"},{"key":"10147_CR43","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1093\/cvr\/cvaa097","volume":"116","author":"R Kreutz","year":"2020","unstructured":"Kreutz, R., Algharably, E. A. E., Azizi, M., Dobrowolski, P., Guzik, T., Januszewicz, A., Persu, A., Prejbisz, A., Riemer, T. G., Wang, J. G., et al. (2020). Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: Implications for COVID-19. Cardiovasc Res, 116, 1688\u20131699. https:\/\/doi.org\/10.1093\/cvr\/cvaa097.","journal-title":"Cardiovasc Res"},{"key":"10147_CR44","doi-asserted-by":"publisher","first-page":"H1084","DOI":"10.1152\/ajpheart.00217.2020","volume":"318","author":"AM South","year":"2020","unstructured":"South, A. M., Diz, D. I., & Chappell, M. C. (2020). COVID-19, ACE2, and the cardiovascular consequences. Am J Physiol Heart Circ Physiol, 318, H1084\u2013H1090. https:\/\/doi.org\/10.1152\/ajpheart.00217.2020.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10147_CR45","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1161\/HYPERTENSIONAHA.120.15082","volume":"75","author":"AHJ Danser","year":"2020","unstructured":"Danser, A. H. J., Epstein, M., & Batlle, D. (2020). Renin-angiotensin system blockers and the COVID-19 pandemic: At present there is no evidence to abandon renin-angiotensin system blockers. Hypertension, 75, 1382\u20131385. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.15082.","journal-title":"Hypertension"},{"key":"10147_CR46","doi-asserted-by":"publisher","first-page":"e00160","DOI":"10.1128\/mSphere.00160-20","volume":"5","author":"L Wahba","year":"2020","unstructured":"Wahba, L., Jain, N., Fire, A. Z., Shoura, M. J., Artiles, K. L., McCoy, M. J., & Jeong, D. E. (2020). An extensive meta-metagenomic search identifies SARS-CoV-2-homologous sequences in pangolin lung viromes. mSphere, 5, e00160\u2013e00120. https:\/\/doi.org\/10.1128\/mSphere.00160-20.","journal-title":"mSphere"},{"key":"10147_CR47","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1056\/NEJMc2005203","volume":"382","author":"BM Henry","year":"2020","unstructured":"Henry, B. M., & Vikse, J. (2020). Clinical characteristics of Covid-19 in China. N Engl J Med, 382, 1860\u20131861. https:\/\/doi.org\/10.1056\/NEJMc2005203.","journal-title":"N Engl J Med"},{"key":"10147_CR48","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.mayocp.2020.03.026","volume":"95","author":"F Sanchis-Gomar","year":"2020","unstructured":"Sanchis-Gomar, F., Lavie, C. J., Perez-Quilis, C., Henry, B. M., & Lippi, G. (2020). Angiotensin-converting enzyme 2 and antihypertensives (angiotensin receptor blockers and angiotensin-converting enzyme inhibitors) in coronavirus disease 2019. Mayo Clin Proc, 95, 1222\u20131230. https:\/\/doi.org\/10.1016\/j.mayocp.2020.03.026.","journal-title":"Mayo Clin Proc"},{"key":"10147_CR49","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.phrs.2016.03.018","volume":"107","author":"E Simoes","year":"2016","unstructured":"Simoes, E., Silva, A. C., & Teixeira, M. M. (2016). ACE inhibition, ACE2 and angiotensin-(1-7) axis in kidney and cardiac inflammation and fibrosis. Pharmacol Res, 107, 154\u2013162. https:\/\/doi.org\/10.1016\/j.phrs.2016.03.018.","journal-title":"Pharmacol Res"},{"issue":"5","key":"10147_CR50","doi-asserted-by":"publisher","first-page":"H958","DOI":"10.1152\/ajpheart.oo723.2018","volume":"316","author":"RAS Santos","year":"2019","unstructured":"Santos, R. A. S., Oudit, G. Y., Verano-Braga, T., Canta, G., Steckelings, U. M., & Bader, M. (2019). The renin-angiotensin system: Going beyond the classical paradigms. Am J Physiol Heart Circ Physiol, 316(5), H958\u2013H970. https:\/\/doi.org\/10.1152\/ajpheart.oo723.2018.","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"3","key":"10147_CR51","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1124\/pr.59.3.3","volume":"59","author":"H Kobori","year":"2007","unstructured":"Kobori, H., Nangaku, M., Navar, L. G., & Nishiyama, A. (2007). The intrarenal renin-angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacol, 59(3), 251\u2013287. https:\/\/doi.org\/10.1124\/pr.59.3.3.","journal-title":"Pharmacol"}],"container-title":["Journal of Cardiovascular Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-021-10147-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12265-021-10147-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12265-021-10147-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T17:29:47Z","timestamp":1648574987000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12265-021-10147-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10147"],"URL":"https:\/\/doi.org\/10.1007\/s12265-021-10147-3","relation":{},"ISSN":["1937-5387","1937-5395"],"issn-type":[{"value":"1937-5387","type":"print"},{"value":"1937-5395","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,1]]},"assertion":[{"value":"7 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The human subject study was approved by the Research Ethics Commission of Jin Yin-Tan Hospital (No.KY-2020-54.01), and the requirement for informed consent was waived by the Ethics Commission of the designated hospital for emerging infectious diseases. Regarding the animal experiments, all the procedures were approved by the Animal Care and Use Committee of the Institute of Laboratory Animal Science, Peking Union Medical College (BLL20001). (See the  for details)","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}