The renin-angiotensin system: An integrated view of lung disease and coagulopathy in COVID-19 and therapeutic implications

Abstract

The renin-angiotensin system (RAS) has long been appreciated as a major regulator of blood pressure, but has more recently been recognized as a mechanism for modulating inflammation as well. While there has been concern in COVID-19 patients over the use of drugs that target this system, the RAS has not been explored fully as a druggable target. The abbreviated description of the RAS suggests that its dysregulation may be at the center of COVID-19.

Figure 1.

The RAS in health and in SARS-CoV-2 infection. Left: In a healthy individual, there is a balance of AT1, AT2, and membrane-bound ACE2 with production of ang1-7. Aldosterone increases Mas expression, and ang1-7 binds Mas to suppress inflammation. Right: In a SARS-CoV-2–infected individual, there is an imbalanced RAS, with viral spike protein causing ACE2 shedding, diminished production of ang1-7, and high AT1 with low AT2.