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

Abstract

Aims Obesity, diabetes and cardiovascular disease are associated with COVID‐19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. Materials and methods Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open‐heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real‐time PCR of ACE1, ACE2 and ADAM17 . From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA. Results Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49‐1.61] vs 1.51 [1.47‐1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65‐1.70] vs 1.70 [1.66‐1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50‐2.28] vs 1.52 [1.49‐1.55] a.u., P = .05 for ACE2 and 1.68 [1.66‐1.78] vs 1.66 [1.63‐1.69] a.u., P < .05 for ADAM17 ). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels ( P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55‐1.63] vs 1 [1‐1.34]), were not correlated with the soluble ACE2. Conclusion Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS‐CoV‐2 infection.

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

“…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.…”

Epicardial adipose tissue in contemporary cardiology

“…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 .…”

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

“…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).…”