The carboxypeptidase ACE2 is a homologue of angiotensin-converting enzyme (ACE). To clarify the physiological roles of ACE2, we generated mice with targeted disruption of the Ace2 gene. ACE2-deficient mice were viable, fertile, and lacked any gross structural abnormalities. We found normal cardiac dimensions and function in ACE2-deficient animals with mixed or inbred genetic backgrounds. On the C57BL/6 background, ACE2 deficiency was associated with a modest increase in blood pressure, whereas the absence of ACE2 had no effect on baseline blood pressures in 129/SvEv mice. After acute Ang II infusion, plasma concentrations of Ang II increased almost 3-fold higher in ACE2-deficient mice than in controls. In a model of Ang II–dependent hypertension, blood pressures were substantially higher in the ACE2-deficient mice than in WT. Severe hypertension in ACE2-deficient mice was associated with exaggerated accumulation of Ang II in the kidney, as determined by MALDI-TOF mass spectrometry. Although the absence of functional ACE2 causes enhanced susceptibility to Ang II–induced hypertension, we found no evidence for a role of ACE2 in the regulation of cardiac structure or function. Our data suggest that ACE2 is a functional component of the renin-angiotensin system, metabolizing Ang II and thereby contributing to regulation of blood pressure.
Susan B. Gurley, Alicia Allred, Thu H. Le, Robert Griffiths, Lan Mao, Nisha Philip, Timothy A. Haystead, Mary Donoghue, Roger E. Breitbart, Susan L. Acton, Howard A. Rockman, Thomas M. Coffman
Title and authors | Publication | Year |
---|---|---|
The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome
C McClenaghan, Y Huang, SJ Matkovich, A Kovacs, CJ Weinheimer, R Perez, TJ Broekelmann, TM Harter, JM Lee, MS Remedi, CG Nichols |
Function | 2020 |
ACE2 mouse models: a toolbox for cardiovascular and pulmonary research
H Jia, X Yue, E Lazartigues |
Nature Communications | 2020 |
Sex-Specific Modulation of Blood Pressure and the Renin-Angiotensin System by ACE (Angiotensin-Converting Enzyme) 2
H Ji, AM de Souza, B Bajaj, W Zheng, X Wu, RC Speth, K Sandberg |
Hypertension | 2020 |
Biological Context Linking Hypertension and Higher Risk for COVID-19 Severity
CA Tavares, MA Bailey, AC Girardi |
Frontiers in physiology | 2020 |
Clinical Implications of SARS-CoV-2 Interaction With Renin Angiotensin System
A Brojakowska, J Narula, R Shimony, J Bander |
Journal of the American College of Cardiology | 2020 |
The ACE2‐deficient mouse: A model for a cytokine storm‐driven inflammation
J Wang, N Kaplan, J Wysocki, W Yang, K Lu, H Peng, D Batlle, RM Lavker |
The FASEB Journal | 2020 |
Recent updates on COVID-19: A holistic review
S Jakhmola, O Indari, D Kashyap, N Varshney, A Rani, C Sonkar, B Baral, S Chatterjee, A Das, R Kumar, HC Jha |
Heliyon | 2020 |
Molecules in pathogenesis: angiotensin converting enzyme 2 (ACE2)
O Wiese, AE Zemlin, TS Pillay |
Journal of clinical pathology | 2020 |
Severe Acute Respiratory Syndrome Coronavirus 2, COVID-19, and the Renin-Angiotensin System: Pressing Needs and Best Research Practices
MA Sparks, AM South, AD Badley, CM Baker-Smith, D Batlle, B Bozkurt, R Cattaneo, SD Crowley, LJ DellItalia, AL Ford, K Griendling, SB Gurley, SE Kasner, JA Murray, KA Nath, MA Pfeffer, J Rangaswami, WR Taylor, VD Garovic |
Hypertension | 2020 |
ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives
F Saponaro, G Rutigliano, S Sestito, L Bandini, B Storti, R Bizzarri, R Zucchi |
Frontiers in Molecular Biosciences | 2020 |
Implications of renal ACE2 expression in the age of COVID-19
HM Salah, JM Arthur, JL Mehta |
European Heart Journal | 2020 |
Angiotensin-converting enzyme 2 influences pancreatic and renal function in diabetic mice
H Roca-Ho, V Palau, J Gimeno, J Pascual, MJ Soler, M Riera |
Laboratory Investigation | 2020 |
COVID-19, Renin-Angiotensin System and Endothelial Dysfunction
R Amraei, N Rahimi |
Cells | 2020 |
Cardiovascular Changes in Patients With COVID-19 From Wuhan, China
L Song, S Zhao, L Wang, K Yang, W Xiao, SP Clifford, J Huang, X Chen |
Frontiers in Cardiovascular Medicine | 2020 |
ACE2 (Angiotensin-Converting Enzyme 2) in Cardiopulmonary Diseases: Ramifications for the Control of SARS-CoV-2
RK Sharma, BR Stevens, AG Obukhov, MB Grant, GY Oudit, Q Li, EM Richards, CJ Pepine, MK Raizada |
Hypertension | 2020 |
Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications
N Banu, SS Panikar, LR Leal, AR Leal |
Life Sciences | 2020 |
Identifying pathophysiological bases of disease in COVID-19
CJ Goldin, R Vázquez, FP Polack, D Alvarez-Paggi |
Translational Medicine Communications | 2020 |
Impaired Breakdown of Bradykinin and Its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection
S de Maat, Q de Mast, AH Danser, FL van de Veerdonk, C Maas |
Seminars in thrombosis and hemostasis | 2020 |
Covid‐19, ACE2 and the kidney
JH Hardenberg, FC Luft |
Acta physiologica (Oxford, England) | 2020 |
The Genetic Dissection of Ace2 Expression Variation in the Heart of Murine Genetic Reference Population
F Xu, J Gao, U Munkhsaikhan, N Li, Q Gu, JF Pierre, A Starlard-Davenport, JA Towbin, Y Cui, E Purevjav, L Lu |
Frontiers in Cardiovascular Medicine | 2020 |
COVID-19 and RAS: Unravelling an Unclear Relationship
D DArdes, A Boccatonda, I Rossi, MT Guagnano, F Santilli, F Cipollone, M Bucci |
International journal of molecular sciences | 2020 |