tetano
Editor, Senior Moderator
Am J Physiol Heart Circ Physiol
. 2020 Oct 9.
doi: 10.1152/ajpheart.00681.2020. Online ahead of print.
Role of angiotensin converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection
Fulton A Robinson[SUP] 1 [/SUP], Ryan P Mihealsick[SUP] 1 [/SUP], Brant M Wagener[SUP] 2 [/SUP], Peter Hanna[SUP] 3 [/SUP], Megan D Poston[SUP] 1 [/SUP], Igor F Efimov[SUP] 4 [/SUP], Kalyanam Shivkumar[SUP] 3 [/SUP], Donald B Hoover[SUP] 1 [/SUP]
Affiliations
Abstract
The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by pre-existing cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang (1-7), but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.
Keywords: ACE2; SARS-CoV-2; cardiac dysfunction; pericyte; renin angiotensin aldosterone system.
. 2020 Oct 9.
doi: 10.1152/ajpheart.00681.2020. Online ahead of print.
Role of angiotensin converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection
Fulton A Robinson[SUP] 1 [/SUP], Ryan P Mihealsick[SUP] 1 [/SUP], Brant M Wagener[SUP] 2 [/SUP], Peter Hanna[SUP] 3 [/SUP], Megan D Poston[SUP] 1 [/SUP], Igor F Efimov[SUP] 4 [/SUP], Kalyanam Shivkumar[SUP] 3 [/SUP], Donald B Hoover[SUP] 1 [/SUP]
Affiliations
- PMID: 33036546
- DOI: 10.1152/ajpheart.00681.2020
Abstract
The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by pre-existing cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang (1-7), but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.
Keywords: ACE2; SARS-CoV-2; cardiac dysfunction; pericyte; renin angiotensin aldosterone system.