Many of us have now heard about ACE2 as the receptor to which the SARS-CoV2 spike protein binds. Thus, it is considered the viral entry point for COVID-19. Other than that, we probably know little more about it.
Angiotensin converting enzyme (ACE) and angiotensin converting enzyme-2 (ACE2) play critical roles in the renin-angiotensin-aldosterone system (RAAS or RAS). To keep it simple, RAAS involves the series of reactions that work to regulate blood pressure. ACE affects vasoconstriction (i.e., tends to increase blood pressure) and ACE2 affects vasodilation (i.e., tends to decrease blood pressure). In a nutshell, a high ACE/ACE2 will promote high blood pressures, and a low ACE/ACE2 will promote low blood pressures. Unfortunately, to fully understand the functions of ACE and ACE2 might require at least one course in microbiology (Samavati and Uhal [2020] and Pagliaro and Penna [2020], however, present pretty good reviews).
A few things of note about ACE2, however, are that it is expressed throughout the body in tissues including liver, intestine, brain, heart, kidneys, and testes, as well as the lungs, and it is affected by age, gender, diet, and physical activity; women tend to have lower ACE/ACE2 ratios than men; and down-regulation of ACE2 (and/or up-regulation of ACE) and ACE/ACE2 imbalances is associated with cigarette smoking, cardiovascular and other pathologies, hypertension, high-sodium and/or high-glucose diets, insulin-resistance, diabetes, and obesity.
While ACE2 provides the coronavirus access to infect the body, it also provides a protective role (anti-inflammatory, anti-oxidant, anti-fibrotic, etc.) in cardiovascular, respiratory, and other tissues. Discussion of these mechanisms are beyond the scope of this blog (and, perhaps, the author’s ability to articulate them), but it is clear that upregulation of ACE2 favors greater protection against symptomatic COVID-19 (and the associated comorbidities). The SARS-CoV2 virus appears to down-regulate ACE2 and exacerbates the “pro-inflammatory milieu of high ACE/ACE2 ratio” (Pagliaro & Penna, 2020).
The interactions are complex, but, suffice it to say, ACE/ACE2 is an important health consideration—not only for COVID-19. There is, of course, a genetic component, but ACE/ACE2 is, above all, an issue of hypokinetic disease and diet. Obesity (albeit avoided in conversation) is a central factor in metabolic syndrome (the co-presence of insulin resistance, hypertension, and elevated triglycerides) and the risk of severe COVID-19 infection and death.
Risk factors for metabolic syndrome include: abdominal obesity (waist circumference >102 cm or 40 for men and >88 cm or 35 for women), high triglycerides (≥150 mg/dl), low HDL cholesterol (<40 mg/dl for men and <50 mg/dl for women), high blood pressure (≥130/85 mm Hg), and high fasting blood glucose (≥110 mg/dl). This would suggest that these are, in turn, risk factors for COVID-19.
Thus, a primary focus on defeating COVID-19—in eliminating severe complications (including long-haul COVID-19) and death—should be on controlling the factors that affect ACE/ACE2. Namely, light must be focused on nutritional and physical activity habits and altering the body composition of Americans. We also need to better understand the genetics behind ACE/ACE2. (Manning and Fink [2020] make an interesting case that will have you looking at your hand [i.e., the ratio of your index finger to your ring finger (2D:4D)]). Regardless of our gender and genetics, we need to become more active, maintain a healthy body composition, and stop eating crappy foods!
Be your best today; be better tomorrow.
Carpe momento!
Manning (2020). Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates. Early Human Development, 146:105074. doi: 10.1016/j.earlhumdev.2020.105074
Pagliaro, P. & Penna, C. (2020). ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)? Frontiers in Medicine, 7:335. doi: 10.3389/fmed.2020.00335
Samavati, L. & Uhal, B.D. (2020). ACE2, Much More Than Just a Receptor for SARS-CoV-2. Frontiers in Cellular and Infection Microbiology, 10:317. doi: 10.3389/fcimb.2020.00317