“The enzyme ADAM-17 is the key to regulating tissue and plasma ACE2 levels. This enzyme, which is thought to be more active in men than women, cleaves tissue ACE2 to form plasma ACE2, and it is believed that the virus responsible for COVID-19 activates ADAM-17,” he noted.
Is COVID-19 Activating the Renin–Angiotensin System?
In an editorial accompanying the European Heart Journal publication, Gavin Oudit, MD, University of Alberta, Edmonton, Canada, and Mark Pfeffer, MD, Brigham and Women’s Hospital, Boston, Massachusetts, suggest that further work should measure plasma angiotensin peptides and plasma ACE2 levels and activity in COVID-19 patients to provide a direct evaluation of the state of the renin–angiotensin system, which could guide therapeutic interventions.
In comments to Medscape Medical News, Oudit, who has researched extensively on ACE2, put forward a hypothesis that the COVID-19 virus could be bringing about its harmful effects by causing an over-activation of the renin–angiotensin system.
Activation of ADAM-17 is detrimental on two levels, Oudit says. “It directly causes a super inflammatory response, and it also reduces cardioprotective ACE2 in tissue.”
Oudit believes ACE2 has been wrongly cast as the villain regarding COVID-19 infection. “Yes, the virus does bind to ACE2 to enter cells, but only a small amount of ACE2 is needed for this. Higher levels are needed to protect from cardiovascular disease.”
“By activating ADAM-17 the virus causes shedding of ACE2 from tissue into plasma, and the reduction of ACE2 in tissue leads to over-activation of the renin–angiotensin system in tissues, which causes cardiovascular disease to get worse,” Oudit explained.
He believes there has been a lot of misinformation surrounding COVID-19, which has included speculation about ACE inhibitors and ARBs. “The science that we know suggests that these drugs are more likely to be beneficial than harmful. Observational clinical studies reported so far support this view.
“As we believe the renin–angiotensin system is being over-activated by the virus, this could also explain why patients with underlying cardiovascular diseases are having worse outcomes and would suggest that taking an ACE inhibitor or ARB would actually be protective.”
On the influenza study, Oudit said: “The influenza virus may well also activate the renin–angiotensin system. That study suggests that ACE inhibitors and ARBs may be protective here as well.”