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ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

ABSTRACT: COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( ACE2 ), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 participants, lower adipose tissue ACE2 expression was associated with adverse cardio-metabolic health indices including type 2 diabetes (T2D) and obesity status, higher serum fasting insulin and BMI, and lower serum HDL levels (P<5.32x10 -4 ). ACE2 expression levels were also associated with estimated proportions of cell types in adipose tissue; lower ACE2 expression was associated with a lower proportion of microvascular endothelial cells (P=4.25x10 -4 ) and higher macrophage proportion (P=2.74x10 -5 ), suggesting a link to inflammation. Despite an estimated heritability of 32%, we did not identify any proximal or distal genetic variants (eQTLs) associated with adipose tissue ACE2 expression. Our results demonstrate that at-risk individuals have lower background ACE2 levels in this highly relevant tissue. Further studies will be required to establish how this may contribute to increased COVID-19 severity.

SUBMITTER: El-Sayed Moustafa JS

PROVIDER: S-EPMC7430606 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

El-Sayed Moustafa Julia S JS Jackson Anne U AU Brotman Sarah M SM Guan Li L Villicaña Sergio S Roberts Amy L AL Zito Antonino A Bonnycastle Lori L Erdos Michael R MR Narisu Narisu N Stringham Heather M HM Welch Ryan R Yan Tingfen T Lakka Timo T Parker Stephen S Tuomilehto Jaakko J Collins Francis S FS Pajukanta Päivi P Boehnke Michael M Koistinen Heikki A HA Laakso Markku M Falchi Mario M Bell Jordana T JT Scott Laura J LJ Mohlke Karen L KL Small Kerrin S KS

medRxiv : the preprint server for health sciences 20200814

COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 ( <i>ACE2</i> ), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 ...[more]

PMID: 32817962

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Project description:High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.

Project description:Background: Myocardial injury is a life-threatening complication of coronavirus disease 2019 (COVID-19). Pre-existing health conditions and early morphological alterations may precipitate cardiac injury and dysfunction after contracting the virus. The current study aimed at assessing potential risk factors for COVID-19 cardiac complications in patients with pre-existing conditions and imaging predictors. Methods and Results: The multi-center, retrospective cohort study consecutively enrolled 400 patients with lab-confirmed COVID-19 in six Chinese hospitals remote to the Wuhan epicenter. Patients were diagnosed with or without the complication of myocardial injury by history and cardiac biomarker Troponin I/T (TnI/T) elevation above the 99th percentile upper reference limit. The majority of COVID-19 patients with myocardial injury exhibited pre-existing health conditions, such as hypertension, diabetes, hypercholesterolemia, and coronary disease. They had increased levels of the inflammatory cytokine interleukin-6 and more in-hospital adverse events (admission to an intensive care unit, invasive mechanical ventilation, or death). Chest CT scan on admission demonstrated that COVID-19 patients with myocardial injury had higher epicardial adipose tissue volume ([EATV] 139.1 (83.8-195.9) vs. 92.6 (76.2-134.4) cm2; P = 0.036). The optimal EATV cut-off value (137.1 cm2) served as a useful factor for assessing myocardial injury, which yielded sensitivity and specificity of 55.0% (95%CI, 32.0-76.2%) and 77.4% (95%CI, 71.6-82.3%) in adverse cardiac events, respectively. Multivariate logistic regression analysis showed that EATV over 137.1 cm2 was a strong independent predictor for myocardial injury in patients with COVID-19 [OR 3.058, (95%CI, 1.032-9.063); P = 0.044]. Conclusions: Augmented EATV on admission chest CT scan, together with the pre-existing health conditions (hypertension, diabetes, and hyperlipidemia) and inflammatory cytokine production, is associated with increased myocardial injury and mortality in COVID-19 patients. Assessment of pre-existing conditions and chest CT scan EATV on admission may provide a threshold point potentially useful for predicting cardiovascular complications of COVID-19.

Dataset Information

ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

Publications

ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition.

Similar Datasets

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