PMC:7161517 / 30613-33323 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7161517","sourcedb":"PMC","sourceid":"7161517","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7161517","text":"Medical Management in Cardiovascular Patients With SARS-CoV-2\nRegardless of how SARS-CoV-2 completes virion assembly, it is clear that membrane-bound ACE2 would play a physiological role in the replication of the novel virus. The question remains whether the use of ACE inhibitors, ARBs, and MRAs should be avoided in the setting of SARS-CoV infection because each agent (42, 43, 44, 45, 46,53) upregulates ACE2 expression and activity.\nLipopolysaccharide-induced acute lung injury mouse models exhibited decreased expression of ACE2, lung and inflammatory injury; however, this was ameliorated by the injection of cells transfected with ACE2 and resulted in the improvement of lung function and lung injury. Treatment of these mice with ACE inhibitors and ARBs also alleviated lipopolysaccharide-induced pneumonic injury (67). Previous studies showed the SARS-CoV S protein can exaggerate acute lung failure through dysregulation of the RAS. However, SARS-CoV Spike–mediated lung failure could be rescued by inhibition of the AT1 receptor (67). Again, adequate data on the effects of RAS inhibition in patients with COVID-19 is not available, and ongoing clinical and/or observations studies are being conducted (see previous mentions of NCT04318301, NCT04318418, NCT04312009, NCT04311177, NCT04287686, NCT04330300, NCT04329195).\nIf SARS-CoV-2 down-regulates membrane-bound ACE2 by promoting the ADAM17−mediated ectodomain shedding, resulting in increased concentrations of soluble ACE2 without compromising viral propagation, we hypothesize this would result in the overall down regulation of the ACE2/Ang1-7/Mas pathway, which would contribute to the severity of inflammation and systemic dysregulation observed in SARS-CoV-2. Thus, in patients with cardiovascular disease and SARS-CoV-2, the use of ACE inhibitors, ARBs, or MRAs may be favorable as a method to endogenously upregulate ACE2 as a compensatory mechanism that provides anti-inflammatory, antifibrotic, and antithrombotic support as well as reduction in progression of vascular and/or cardiac remodeling and heart failure. Several societies, including the American College of Cardiology, American Heart Association, Heart Failure Society of America (68), and European Society of Cardiology (69) have recommended continuing RAS antagonists because of the lack of conclusive data on a link between upregulation of systemic or tissue ACE2 and the increased susceptibility to COVID-19 in patients with cardiovascular disease. Based on our review, we hypothesize cardiovascular patients with COVID-19 should remain on RAS inhibitors because of the protective effects of the ACE2 pathway until RAS blockade is proven to increase the risk of COVID-19.","divisions":[{"label":"title","span":{"begin":0,"end":61}},{"label":"p","span":{"begin":62,"end":436}},{"label":"p","span":{"begin":437,"end":1330}}],"tracks":[{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T185","span":{"begin":437,"end":455},"obj":"Body_part"},{"id":"T186","span":{"begin":470,"end":474},"obj":"Body_part"},{"id":"T187","span":{"begin":535,"end":539},"obj":"Body_part"},{"id":"T188","span":{"begin":615,"end":620},"obj":"Body_part"},{"id":"T189","span":{"begin":678,"end":682},"obj":"Body_part"},{"id":"T190","span":{"begin":696,"end":700},"obj":"Body_part"},{"id":"T191","span":{"begin":778,"end":796},"obj":"Body_part"},{"id":"T192","span":{"begin":867,"end":874},"obj":"Body_part"},{"id":"T193","span":{"begin":896,"end":900},"obj":"Body_part"},{"id":"T194","span":{"begin":976,"end":980},"obj":"Body_part"},{"id":"T195","span":{"begin":2074,"end":2079},"obj":"Body_part"},{"id":"T196","span":{"begin":2163,"end":2168},"obj":"Body_part"},{"id":"T197","span":{"begin":2182,"end":2187},"obj":"Body_part"},{"id":"T198","span":{"begin":2390,"end":2396},"obj":"Body_part"}],"attributes":[{"id":"A185","pred":"fma_id","subj":"T185","obj":"http://purl.org/sig/ont/fma/fma82785"},{"id":"A186","pred":"fma_id","subj":"T186","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A187","pred":"fma_id","subj":"T187","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A188","pred":"fma_id","subj":"T188","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A189","pred":"fma_id","subj":"T189","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A190","pred":"fma_id","subj":"T190","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A191","pred":"fma_id","subj":"T191","obj":"http://purl.org/sig/ont/fma/fma82785"},{"id":"A192","pred":"fma_id","subj":"T192","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A193","pred":"fma_id","subj":"T193","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A194","pred":"fma_id","subj":"T194","obj":"http://purl.org/sig/ont/fma/fma7195"},{"id":"A195","pred":"fma_id","subj":"T195","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A196","pred":"fma_id","subj":"T196","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A197","pred":"fma_id","subj":"T197","obj":"http://purl.org/sig/ont/fma/fma7088"},{"id":"A198","pred":"fma_id","subj":"T198","obj":"http://purl.org/sig/ont/fma/fma9637"},{"subj":"T185","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T186","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T187","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T188","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T189","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T190","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T191","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T192","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T193","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T194","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T195","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T196","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T197","pred":"source","obj":"LitCovid-PD-FMA-UBERON"},{"subj":"T198","pred":"source","obj":"LitCovid-PD-FMA-UBERON"}]},{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T77","span":{"begin":470,"end":474},"obj":"Body_part"},{"id":"T78","span":{"begin":535,"end":539},"obj":"Body_part"},{"id":"T79","span":{"begin":678,"end":682},"obj":"Body_part"},{"id":"T80","span":{"begin":696,"end":700},"obj":"Body_part"},{"id":"T81","span":{"begin":896,"end":900},"obj":"Body_part"},{"id":"T82","span":{"begin":938,"end":941},"obj":"Body_part"},{"id":"T83","span":{"begin":976,"end":980},"obj":"Body_part"},{"id":"T84","span":{"begin":1085,"end":1088},"obj":"Body_part"},{"id":"T85","span":{"begin":2074,"end":2079},"obj":"Body_part"},{"id":"T86","span":{"begin":2163,"end":2168},"obj":"Body_part"},{"id":"T87","span":{"begin":2182,"end":2187},"obj":"Body_part"},{"id":"T88","span":{"begin":2289,"end":2292},"obj":"Body_part"},{"id":"T89","span":{"begin":2390,"end":2396},"obj":"Body_part"},{"id":"T90","span":{"begin":2579,"end":2582},"obj":"Body_part"},{"id":"T91","span":{"begin":2654,"end":2657},"obj":"Body_part"}],"attributes":[{"id":"A77","pred":"uberon_id","subj":"T77","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A78","pred":"uberon_id","subj":"T78","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A79","pred":"uberon_id","subj":"T79","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A80","pred":"uberon_id","subj":"T80","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A81","pred":"uberon_id","subj":"T81","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A82","pred":"uberon_id","subj":"T82","obj":"http://purl.obolibrary.org/obo/UBERON_0018229"},{"id":"A83","pred":"uberon_id","subj":"T83","obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"A84","pred":"uberon_id","subj":"T84","obj":"h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