Effects of PM2.5 Exposure on the ACE/ACE2 Pathway: Possible Implication in COVID-19 Pandemic

Abstract

Particulate matter (PM) is a harmful component of urban air pollution and PM2.5, in particular, can settle in the deep airways. The RAS system plays a crucial role in the pathogenesis of pollution-induced inflammatory diseases: the ACE/AngII/AT1 axis activates a pro-inflammatory pathway counteracted by the ACE2/Ang(1-7)/MAS axis, which in turn triggers an anti-inflammatory and protective pathway. However, ACE2 acts also as a receptor through which SARS-CoV-2 penetrates host cells to replicate. COX-2, HO-1, and iNOS are other crucial proteins involved in ultrafine particles (UFP)-induced inflammation and oxidative stress, but closely related to the course of the COVID-19 disease. BALB/c male mice were subjected to PM2.5 sub-acute exposure to study its effects on ACE2 and ACE, COX-2, HO-1 and iNOS proteins levels, in the main organs concerned with the pathogenesis of COVID-19. The results obtained show that sub-acute exposure to PM2.5 induces organ-specific modifications which might predispose to greater susceptibility to severe symptomatology in the case of SARS-CoV-2 infection. The novelty of this work consists in using a molecular study, carried out in the lung but also in the main organs involved in the disease, to analyze the close relationship between exposure to pollution and the pathogenesis of COVID-19.

Causal relationship between particulate matter and COVID-19 risk: A mendelian randomization study

“…Particulate matter with aerodynamic diameters less than 2.5 μm can readily travel through the respiratory tract to reach type II alveolar cells, where SARS-CoV-2 can bind to angiotensin‐converting enzyme 2 (ACE2) receptor to infect the cells. A murine study indicated that PM2.5 disrupted the balance between ACE and ACE2 in the liver and brain, consequently diminishing the protective effects of the ACE2/Angiotensin 1-7/MAS pathway [ 38 ]. Additionally, PM2.5 exposure was observed to increase the expression of cyclooxygenase-2 (COX-2) in both lung and heart.…”

Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta

“…An increased expression of ACE1 relative to ACE2 has been associated with inflammation and various pathologies' morbidity. Indeed, an imbalance in the ACE1/ACE2 ratio may result in increased blood pressure, inflammation, and susceptibility to COVID-19 infection [38,39]. Therefore, we analyzed the ACE1/ACE2 ratio in function to the exposure of cells to different calcitriol concentrations.…”