PMID- 34361021
OWN - NLM
STAT- MEDLINE
DCOM- 20210826
LR  - 20240403
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 15
DP  - 2021 Jul 31
TI  - Role of the Renin-Angiotensin-Aldosterone and Kinin-Kallikrein Systems in the 
      Cardiovascular Complications of COVID-19 and Long COVID.
LID - 10.3390/ijms22158255 [doi]
LID - 8255
AB  - 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-Angiotensin-Aldosterone System (RAAS) 
      and Kinin-Kallikrein 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.
FAU - Cooper, Samantha L
AU  - Cooper SL
AD  - Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
AD  - Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
FAU - Boyle, Eleanor
AU  - Boyle E
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Jefferson, Sophie R
AU  - Jefferson SR
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Heslop, Calum R A
AU  - Heslop CRA
AUID- ORCID: 0000-0001-6066-3410
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Mohan, Pirathini
AU  - Mohan P
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Mohanraj, Gearry G J
AU  - Mohanraj GGJ
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Sidow, Hamza A
AU  - Sidow HA
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Tan, Rory C P
AU  - Tan RCP
AD  - School of Medicine, Queen's Medical Centre, University of Nottingham, Nottingham 
      NG7 2UH, UK.
FAU - Hill, Stephen J
AU  - Hill SJ
AUID- ORCID: 0000-0002-4424-239X
AD  - Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
AD  - Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
FAU - Woolard, Jeanette
AU  - Woolard J
AUID- ORCID: 0000-0001-5406-6847
AD  - Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
AD  - Centre of Membrane Proteins and Receptors (COMPARE), School of Life Sciences, 
      University of Nottingham, Nottingham NG7 2UH, UK.
LA  - eng
GR  - MR/N020081/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20210731
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2/metabolism
MH  - Bradykinin/metabolism
MH  - COVID-19/*complications
MH  - Cardiovascular Diseases/drug therapy/*etiology
MH  - Cytokine Release Syndrome/etiology/metabolism
MH  - Humans
MH  - *Kallikrein-Kinin System
MH  - *Renin-Angiotensin System
MH  - Post-Acute COVID-19 Syndrome
MH  - COVID-19 Drug Treatment
PMC - PMC8347967
OTO - NOTNLM
OT  - COVID-19
OT  - cardiovascular system
OT  - kinin-kallikrein system
OT  - long COVID
OT  - renin-angiotensin-aldosterone system
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/08 06:00
MHDA- 2021/08/27 06:00
PMCR- 2021/07/31
CRDT- 2021/08/07 01:08
PHST- 2021/07/04 00:00 [received]
PHST- 2021/07/29 00:00 [revised]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/08/07 01:08 [entrez]
PHST- 2021/08/08 06:00 [pubmed]
PHST- 2021/08/27 06:00 [medline]
PHST- 2021/07/31 00:00 [pmc-release]
AID - ijms22158255 [pii]
AID - ijms-22-08255 [pii]
AID - 10.3390/ijms22158255 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 31;22(15):8255. doi: 10.3390/ijms22158255.