Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity
- 8 October 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in International Journal of Obesity
- Vol. 46 (1), 238-241
- https://doi.org/10.1038/s41366-021-00984-2
Abstract
Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to angiotensin 1–7 the latter having cardioprotective and vasorelaxation effects. Quantitative real-time PCR analysis of plasma samples for circulating miRNAs showed upregulation of miR-200c and miR-let-7b in otherwise healthy individuals with obesity. This was associated with significant downregulation of ACE2, a direct target for both miRNAs, in individuals with obesity. Correlation analysis confirmed a significant negative correlation between ACE2 and both the miRNAs. Studies showed that despite being the functional receptor, inhibition/downregulation of ACE2 did not reduce the severity of COVID-19 infection. In contrast, increased angiotensin II following inhibition of ACE2 may increase the severity of the disease. Taken together, our novel results identify that upregulation of miR-200c may increase the susceptibility of individuals with obesity to COVID-19. Considering miRNA are the earliest molecular regulators, the level of circulating miR-200c could be a potential biomarker in the early identification of those at the risk of severe COVID-19.This publication has 25 references indexed in Scilit:
- Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cellsCell Death & Differentiation, 2018
- Characterization of ACE and ACE2 Expression within Different Organs of the NOD MouseInternational Journal of Molecular Sciences, 2017
- Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participantsThe Lancet, 2016
- The miR-200 Family and Its Targets Regulate Type II Cell Differentiation in Human Fetal LungOnline Journal of Public Health Informatics, 2015
- Overweight and Obesity: Prevalence, Consequences, and Causes of a Growing Public Health ProblemCurrent Obesity Reports, 2015
- miR-141 and miR-200c as Markers of Overall Survival in Early Stage Non-Small Cell Lung Cancer AdenocarcinomaPLOS ONE, 2014
- Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart diseaseCardiovascular Diabetology, 2014
- Increased Circulating ANG II and TNF-α Represents Important Risk Factors in Obese Saudi Adults with Hypertension Irrespective of Diabetic Status and BMIPLOS ONE, 2012
- The incidence of co-morbidities related to obesity and overweight: A systematic review and meta-analysisBMC Public Health, 2009
- Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirusNature, 2003