{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:46:25Z","timestamp":1792791985795,"version":"4.5.0"},"reference-count":181,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N020081\/1"],"award-info":[{"award-number":["MR\/N020081\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the COVID-19 pandemic. Patients may present as asymptomatic or demonstrate mild to severe and life-threatening symptoms. Although COVID-19 has a respiratory focus, there are major cardiovascular complications (CVCs) associated with infection. The reported CVCs include myocarditis, heart failure, arrhythmias, thromboembolism and blood pressure abnormalities. These occur, in part, because of dysregulation of the Renin\u2013Angiotensin\u2013Aldosterone System (RAAS) and Kinin\u2013Kallikrein System (KKS). A major route by which SARS-CoV-2 gains cellular entry is via the docking of the viral spike (S) protein to the membrane-bound angiotensin converting enzyme 2 (ACE2). The roles of ACE2 within the cardiovascular and immune systems are vital to ensure homeostasis. The key routes for the development of CVCs and the recently described long COVID have been hypothesised as the direct consequences of the viral S protein\/ACE2 axis, downregulation of ACE2 and the resulting damage inflicted by the immune response. Here, we review the impact of COVID-19 on the cardiovascular system, the mechanisms by which dysregulation of the RAAS and KKS can occur following virus infection and the future implications for pharmacological therapies.<\/jats:p>","DOI":"10.3390\/ijms22158255","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"8255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Role of the Renin\u2013Angiotensin\u2013Aldosterone and Kinin\u2013Kallikrein Systems in the Cardiovascular Complications of COVID-19 and Long COVID"],"prefix":"10.3390","volume":"22","author":[{"given":"Samantha L.","family":"Cooper","sequence":"first","affiliation":[{"name":"Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Boyle","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8591-3281","authenticated-orcid":false,"given":"Sophie R.","family":"Jefferson","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-3410","authenticated-orcid":false,"given":"Calum R. A.","family":"Heslop","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirathini","family":"Mohan","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gearry G. J.","family":"Mohanraj","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza A.","family":"Sidow","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory C. P.","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-239X","authenticated-orcid":false,"given":"Stephen J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5406-6847","authenticated-orcid":false,"given":"Jeanette","family":"Woolard","sequence":"additional","affiliation":[{"name":"Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"},{"name":"Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"China Novel Coronavirus Investigating and Research Team. 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