Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease

Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to...

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Main Authors: Hui Yin Lim, Sheila K. Patel, Ping Huang, Mark Tacey, Kay Weng Choy, Julie Wang, Geoffrey Donnan, Harshal H. Nandurkar, Prahlad Ho, Louise M. Burrell
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/12/9/1495
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author Hui Yin Lim
Sheila K. Patel
Ping Huang
Mark Tacey
Kay Weng Choy
Julie Wang
Geoffrey Donnan
Harshal H. Nandurkar
Prahlad Ho
Louise M. Burrell
author_facet Hui Yin Lim
Sheila K. Patel
Ping Huang
Mark Tacey
Kay Weng Choy
Julie Wang
Geoffrey Donnan
Harshal H. Nandurkar
Prahlad Ho
Louise M. Burrell
author_sort Hui Yin Lim
collection DOAJ
description Angiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (<i>n</i> = 123; mean age 41 ± 17 years; 35% male) and in patients with cardiovascular risk factors and/or disease (<i>n</i> = 258; mean age 65 ± 14 years; 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, <i>p</i> < 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum amplitude (<i>p</i> < 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (<i>p</i> = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (<i>p</i> < 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis.
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spelling doaj.art-96577ff31e2a43ff9070e4f7140b1a842023-11-23T17:14:08ZengMDPI AGJournal of Personalized Medicine2075-44262022-09-01129149510.3390/jpm12091495Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or DiseaseHui Yin Lim0Sheila K. Patel1Ping Huang2Mark Tacey3Kay Weng Choy4Julie Wang5Geoffrey Donnan6Harshal H. Nandurkar7Prahlad Ho8Louise M. Burrell9Northern Pathology Victoria, Northern Health, Epping, Melbourne, VIC 3076, AustraliaDepartment of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, AustraliaDepartment of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, AustraliaThe Northern Hospital, Epping, VIC 3076, AustraliaNorthern Pathology Victoria, Northern Health, Epping, Melbourne, VIC 3076, AustraliaNorthern Pathology Victoria, Northern Health, Epping, Melbourne, VIC 3076, AustraliaThe Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC 3052, AustraliaAustralian Centre for Blood Diseases, Monash University, Melbourne VIC 3004, AustraliaNorthern Pathology Victoria, Northern Health, Epping, Melbourne, VIC 3076, AustraliaDepartment of Medicine, Austin Health, University of Melbourne, Heidelberg, Melbourne, VIC 3084, AustraliaAngiotensin converting enzyme 2 (ACE2) is an endogenous negative regulator of the renin-angiotensin system, a key factor in the development of cardiovascular disease (CVD). ACE2 is also used by SARS-CoV-2 for host cell entry. Given that COVID-19 is associated with hypercoagulability, it is timely to explore the potential relationship between plasma ACE2 activity and the coagulation profile. In this cross-sectional study, ACE2 activity and global coagulation assays (GCA) including thromboelastography, thrombin, and fibrin generation were measured in adult healthy controls (<i>n</i> = 123; mean age 41 ± 17 years; 35% male) and in patients with cardiovascular risk factors and/or disease (<i>n</i> = 258; mean age 65 ± 14 years; 55% male). ACE2 activity was significantly lower in controls compared to patients with cardiovascular risk factors and/or disease (median 0.10 (0.02, 3.33) vs. 5.99 (1.95, 10.37) pmol/mL/min, <i>p</i> < 0.001). Of the healthy controls, 48% had undetectable ACE2 activity. Controls with detectable ACE2 had lower maximum amplitude (<i>p</i> < 0.001). In patients with cardiovascular risk factors and/or disease, those in the 3rd tertile were older and male (<i>p</i> = 0.002), with a higher Framingham grade and increased number of cardiovascular risk factors (<i>p</i> < 0.001). In conclusion, plasma ACE2 activity is undetectable to very low in young healthy controls with minimal clinically relevant associations to GCA. Patients with cardiovascular risk factors and/or disease have increased plasma ACE2 activity, suggesting that it may be an important biomarker of endothelial dysfunction and atherosclerosis.https://www.mdpi.com/2075-4426/12/9/1495angiotensin converting enzyme 2coagulationcardiovascular diseaserenin angiotensin system
spellingShingle Hui Yin Lim
Sheila K. Patel
Ping Huang
Mark Tacey
Kay Weng Choy
Julie Wang
Geoffrey Donnan
Harshal H. Nandurkar
Prahlad Ho
Louise M. Burrell
Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
Journal of Personalized Medicine
angiotensin converting enzyme 2
coagulation
cardiovascular disease
renin angiotensin system
title Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
title_full Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
title_fullStr Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
title_full_unstemmed Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
title_short Plasma Angiotensin Converting Enzyme 2 (ACE2) Activity in Healthy Controls and Patients with Cardiovascular Risk Factors and/or Disease
title_sort plasma angiotensin converting enzyme 2 ace2 activity in healthy controls and patients with cardiovascular risk factors and or disease
topic angiotensin converting enzyme 2
coagulation
cardiovascular disease
renin angiotensin system
url https://www.mdpi.com/2075-4426/12/9/1495
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