Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer

Couselo‐Seijas, Marinela; Almengló, Cristina; Agra-Bermejo, Rosa; Fernández, Ángel L.; Álvarez, Ezequiel; González-Juanàtey, José Ramón; Eiras, Sonia

doi:10.1111/eci.13463

Cited by 28 publications

(29 citation statements)

References 44 publications

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“…A study on EAT and SAT biopsies from 43 patients who underwent open-heart surgery identified higher levels of ACE2 (p < 0.05) but lower ADAM-17 (p < 0.001), with its cleavage enzyme in EAT compared with subcutaneous fat. Obesity and T2D exacerbated this difference in patients with cardiovascular disease (103). In an animal study, ACE2 was upregulated in murine EAT in association with highfat diet.…”

Section: Visceral Adipose Tissue and Epicardial Adipose Tissue As Markers Of Myocardial Injurymentioning

confidence: 96%

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

Lasbleiz

Gaborit

Soghomonian³

et al. 2021

Front. Endocrinol.

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In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the “cytokine storm” and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.

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Section: Visceral Adipose Tissue and Epicardial Adipose Tissue As Markers Of Myocardial Injurymentioning

confidence: 96%

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

Lasbleiz

Gaborit

Soghomonian³

et al. 2021

Front. Endocrinol.

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“…Angiotensin-converting enzyme 2 (ACE2), which is widely recognized as the entry receptor for SARS-CoV-2 into host cells 152 , is expressed in human EAT 133 . The downregulation of ACE2 levels increases EAT inflammation, whereas treatment with angiotensin 1–7 reduced EAT inflammatory cytokines in a mouse model 153 .…”

Section: Eat and Covid-19mentioning

confidence: 99%

Epicardial adipose tissue in contemporary cardiology

2022

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Interest in epicardial adipose tissue (EAT) is growing rapidly, and research in this area appeals to a broad, multidisciplinary audience. EAT is unique in its anatomy and unobstructed proximity to the heart and has a transcriptome and secretome very different from that of other fat depots. EAT has physiological and pathological properties that vary depending on its location. It can be highly protective for the adjacent myocardium through dynamic brown fat-like thermogenic function and harmful via paracrine or vasocrine secretion of pro-inflammatory and profibrotic cytokines. EAT is a modifiable risk factor that can be assessed with traditional and novel imaging techniques. Coronary and left atrial EAT are involved in the pathogenesis of coronary artery disease and atrial fibrillation, respectively, and it also contributes to the development and progression of heart failure. In addition, EAT might have a role in coronavirus disease 2019 (COVID-19)-related cardiac syndrome. EAT is a reliable potential therapeutic target for drugs with cardiovascular benefits such as glucagon-like peptide 1 receptor agonists and sodium–glucose co-transporter 2 inhibitors. This Review provides a comprehensive and up-to-date overview of the role of EAT in cardiovascular disease and highlights the translational nature of EAT research and its applications in contemporary cardiology.

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“…This is not to be equated with enzyme activity. However, other studies have also investigated ADAM10 and ADAM17 only on gene expression level, as evidence suggests that their gene expression correlates with their activity (Kinoshita et al, 2013;Cheng et al, 2021;Couselo-Seijas et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Autophagy Induces Expression of IL-6 in Human Periodontal Ligament Fibroblasts Under Mechanical Load and Overload and Effects Osteoclastogenesis in vitro

et al. 2021

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Objective: Autophagy is an important cellular adaptation mechanism to mechanical stress. In animal experiments, inhibition of autophagy during orthodontic tooth movement triggered increased expression of inflammation-related genes and decreased bone density. The aim of this study was to investigate how autophagy affects cytokine levels of interleukin 6 (IL-6) in human periodontal ligament (hPDL) fibroblasts under mechanical pressure and the resulting influence on osteoblast communication.Methods: hPDL fibroblasts were subjected to physiologic mechanical load, constant overload, or rapamycin treatment for 16 to 24 h ± autophagy inhibitor 3-MA. Autophagosomes were quantified by flow cytometry. Gene expression of il-6 as well as IL-6 levels in the supernatant were determined with rtPCR and ELISA. To investigate the influence of mechanically-induced autophagy on cell-cell communication, an osteoblast-culture was subjected to supernatant from stimulated hPDL fibroblasts ± soluble IL-6 receptor (sIL-6R). After 24 h, osteoprotegerin (opg) and receptor activator of nuclear factor κB ligand (rankl) gene expressions were detected with rtPCR. Gene expression of a disintegrin and metalloproteinases (adam) 10 and 17 in stimulated hPDL fibroblasts was examined via rtPCR.Results: Autophagy was induced by biomechanical stress in hPDL fibroblasts in a dose-dependent manner. Mechanical load and overload increased IL-6 expression at gene and protein level. Autophagy inhibition further enhanced the effects of mechanical stimulation on IL-6 expression. Mechanical stimulation of hPDL fibroblasts downregulated adam10 and adam17 expressions. Inhibition of autophagy had stimulus-intensity depending effects: autophagy inhibition alone or additional application of physiological stress enhanced adam10 and adam17 expressions, whereas mechanical overload had adverse effects. Osteoblasts showed significantly reduced opg expression in the presence of supernatant derived of hPDL fibroblasts treated with autophagy inhibitor and sIL-6R.Conclusion: IL-6 levels were increased in response to pressure in hPDL fibroblasts, which was further enhanced by autophagy inhibition. This caused a decrease in opg expression in osteoblasts. This may serve as an explanatory model for accelerated tooth movement observed under autophagy inhibition, but may also represent a risk factor for uncontrolled bone loss.

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Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer

Cited by 28 publications

References 44 publications

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

COVID-19 and Obesity: Role of Ectopic Visceral and Epicardial Adipose Tissues in Myocardial Injury

Epicardial adipose tissue in contemporary cardiology

Autophagy Induces Expression of IL-6 in Human Periodontal Ligament Fibroblasts Under Mechanical Load and Overload and Effects Osteoclastogenesis in vitro

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