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{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7161517","sourcedb":"PMC","sourceid":"7161517","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7161517","text":"The novel coronavirus disease-2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), originated from the Wuhan, Hubei providence in central China in December 2019 and was declared a pandemic by the World Health Organization on March 11, 2020 (1). Compared with SARS-CoV, which caused the 2002 to 2003 outbreak, SARS-CoV-2 appears to have a stronger rate of transmission. Although the SARS infection exhibits a prolonged clinical course predominantly involving respiratory manifestations, the clinical course of the novel coronavirus is unclear. Further clinical insights from Wuhan suggest that some patients with COVID-19 exhibit severe cardiovascular damage, and those with underlying cardiovascular disease appear to have an increased risk of death (1,2). Both SARS-CoV and CoV2 belong to the beta-coronavirus phylogeny (3). Although bats may be natural reservoirs for SARS-like coronavirus (3), interspecies transfer of SARS-CoV and SARS-CoV-2 could have occurred through civets (4) and pangolins (5), respectively. Both SARS-CoV strains have been identified to use the angiotensin-converting enzyme 2 (ACE2) receptor as the portal of entry into the affected cell (1,4). ACE2 is a key modulator of the renin-angiotensin system (RAS), which is a signaling pathway involved in the regulation of vascular function, including the regulation of blood pressure, natriuresis, and blood volume control (6). Normally, the RAS involves the formation of angiotensin II (Ang II) through ACE, which contributes to multiple cardiovascular physiological and pathophysiological functions, including hypertension, myocardial hypertrophy, cardiac fibrosis, inflammation, vascular remodeling, and atherosclerosis (7, 8, 9). Because of the adverse cardiovascular effects of RAS upregulation, its inhibition through ACE inhibitors, angiotensin II receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) has been critical for the management of various cardiovascular diseases. In the last 2 decades, the identification of ACE2 and its involvement in the counter regulation of the classic RAS has offered a potentially new therapeutic target (10, 11, 12). ACE2 exists both as membrane-bound and soluble forms, the former of which mediates SARS-CoV-2 infection via S-protein binding (13,14). It is unclear whether SARS-CoV-2 interferes with ACE2 in a manner that contributes to the pathogenesis of SARS or the cardiovascular damage observed (1,2). This raises the question of whether RAS inhibition in cardiovascular patients should be reassessed in the setting of this novel coronavirus.","tracks":[{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T5","span":{"begin":1206,"end":1210},"obj":"Body_part"},{"id":"T6","span":{"begin":1387,"end":1392},"obj":"Body_part"},{"id":"T7","span":{"begin":1420,"end":1425},"obj":"Body_part"},{"id":"T8","span":{"begin":2310,"end":2317},"obj":"Body_part"}],"attributes":[{"id":"A5","pred":"fma_id","subj":"T5","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A6","pred":"fma_id","subj":"T6","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A7","pred":"fma_id","subj":"T7","obj":"http://purl.org/sig/ont/fma/fma9670"},{"id":"A8","pred":"fma_id","subj":"T8","obj":"http://purl.org/sig/ont/fma/fma67257"},{"subj":"T5","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T6","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T7","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T8","pred":"source","obj":"LitCovid-PD-FMA-UBERON"}]},{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T6","span":{"begin":1249,"end":1273},"obj":"Body_part"},{"id":"T7","span":{"begin":1275,"end":1278},"obj":"Body_part"},{"id":"T8","span":{"begin":1387,"end":1392},"obj":"Body_part"},{"id":"T9","span":{"begin":1420,"end":1425},"obj":"Body_part"},{"id":"T10","span":{"begin":1460,"end":1463},"obj":"Body_part"},{"id":"T11","span":{"begin":1801,"end":1804},"obj":"Body_part"},{"id":"T12","span":{"begin":2133,"end":2136},"obj":"Body_part"},{"id":"T13","span":{"begin":2527,"end":2530},"obj":"Body_part"}],"attributes":[{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A11","pred":"uberon_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A13","pred":"uberon_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"subj":"T6","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T7","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T8","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T9","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T10","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T11","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T12","pred":"source","obj":"LitCovid-PD-UBERON"},{"subj":"T13","pred":"source","obj":"LitCovid-PD-UBERON"}]},{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T15","span":{"begin":10,"end":34},"obj":"Disease"},{"id":"T16","span":{"begin":36,"end":44},"obj":"Disease"},{"id":"T17","span":{"begin":66,"end":113},"obj":"Disease"},{"id":"T18","span":{"begin":66,"end":99},"obj":"Disease"},{"id":"T19","span":{"begin":115,"end":123},"obj":"Disease"},{"id":"T20","span":{"begin":304,"end":312},"obj":"Disease"},{"id":"T21","span":{"begin":354,"end":362},"obj":"Disease"},{"id":"T22","span":{"begin":427,"end":431},"obj":"Disease"},{"id":"T23","span":{"begin":432,"end":441},"obj":"Disease"},{"id":"T24","span":{"begin":657,"end":665},"obj":"Disease"},{"id":"T25","span":{"begin":730,"end":752},"obj":"Disease"},{"id":"T26","span":{"begin":807,"end":815},"obj":"Disease"},{"id":"T27","span":{"begin":915,"end":919},"obj":"Disease"},{"id":"T28","span":{"begin":967,"end":975},"obj":"Disease"},{"id":"T29","span":{"begin":980,"end":988},"obj":"Disease"},{"id":"T30","span":{"begin":1068,"end":1076},"obj":"Disease"},{"id":"T31","span":{"begin":1630,"end":1642},"obj":"Disease"},{"id":"T32","span":{"begin":1686,"end":1698},"obj":"Disease"},{"id":"T33","span":{"begin":1725,"end":1740},"obj":"Disease"},{"id":"T34","span":{"begin":1997,"end":2020},"obj":"Disease"},{"id":"T35","span":{"begin":2283,"end":2291},"obj":"Disease"},{"id":"T36","span":{"begin":2294,"end":2303},"obj":"Disease"},{"id":"T37","span":{"begin":2357,"end":2365},"obj":"Disease"},{"id":"T38","span":{"begin":2441,"end":2445},"obj":"Disease"}],"attributes":[{"id":"A15","pred":"mondo_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/MONDO_0100096"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A19","pred":"mondo_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A20","pred":"mondo_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A21","pred":"mondo_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/MONDO_0005091"},{"id":"A22","pred":"mondo_id","subj":"T22","obj":"http://purl.oboli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