Increased Hepatic ACE2 Expression in NAFL and Diabetes—A Risk for COVID-19 Patients?

Soldo, Jelena; Heni, Martin; Königsrainer, Alfred; Häring, Hans‐Ulrich; Birkenfeld, Andreas L.

doi:10.2337/dc20-1458

Cited by 28 publications

(26 citation statements)

References 5 publications

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“…Furthermore, a Mendelian Randomization study indicated that diabetes was causally related to increased ACE2 expression in lung tissue (91). An increase in ACE2 expression was also recently reported in the kidney of patients with diabetic kidney disease (92) and in the liver of patients with diabetes and also subjects with non-alcoholic fatty liver, which is prevalent in subjects with prediabetes (93). The weight of evidence therefore suggests that ACE2 levels are probably increased in various tissues in humans with diabetes and as evidence from cell biology suggests this may increase viral entry, this implies that infection with SARS-CoV-2 may be increased in tissues such as the lung, liver and kidney.…”

Section: Angiotensin Converting Enzyme 2 (Ace2)mentioning

confidence: 71%

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

et al. 2020

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The pandemic of COVID-19, caused by the coronavirus, SARS-CoV-2, has had a global impact not seen for an infectious disease for over a century. This acute pandemic has spread from the East and has been overlaid onto a slow pandemic of metabolic diseases of obesity and diabetes consequent from the increasing adoption of a Western-lifestyle characterized by excess calorie consumption with limited physical activity. It has become clear that these conditions predispose individuals to a more severe COVID-19 with increased morbidity and mortality. There are many features of diabetes and obesity that may accentuate the clinical response to SARS-CoV-2 infection: including an impaired immune response, an atherothrombotic state, accumulation of advanced glycation end products and a chronic inflammatory state. These could prime an exaggerated cytokine response to viral infection, predisposing to the cytokine storm that triggers progression to septic shock, acute respiratory distress syndrome, and multi-organ failure. Infection leads to an inflammatory response and tissue damage resulting in increased metabolic activity and an associated increase in the mechanisms by which cells ingest and degrade tissue debris and foreign materials. It is becoming clear that viruses have acquired an ability to exploit these mechanisms to invade cells and facilitate their own life-cycle. In obesity and diabetes these mechanisms are chronically activated due to the deteriorating metabolic state and this may provide an increased opportunity for a more profound and sustained viral infection.

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Section: Angiotensin Converting Enzyme 2 (Ace2)mentioning

confidence: 71%

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

et al. 2020

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“…Patients with diabetes exhibit increased expression of ACE2 protein in bronchioles and alveoli, 12 as well as liver. 13 The retinal involvement of SARS-CoV-2 has drawn increasing attention. COVID-19 is well known to induce systemic damage beyond respiratory manifestations, 14 leading to enhanced understanding of this condition as a multiorgan disease, 14 affecting the brain, heart, kidney, digestive system, as well as the ocular surface.…”

mentioning

confidence: 99%

Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes—Implications for Retinopathy

Zhou

Guerra

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the expression of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 in human retina. METHODS.Human post-mortem eyes from 13 non-diabetic control cases and 11 diabetic retinopathy cases were analyzed for the expression of ACE2. To compare the vascular ACE2 expression between different organs that involve in diabetes, the expression of ACE2 was investigated in renal specimens from nondiabetic and diabetic nephropathy patients. Expression of TMPRSS2, a cell-surface protease that facilitates SARS-CoV-2 entry, was also investigated in human nondiabetic retinas. Primary human retinal endothelial cells (HRECs) and primary human retinal pericytes (HRPCs) were further used to confirm the vascular ACE2 expression in human retina. RESULTS.We found that ACE2 was expressed in multiple nonvascular neuroretinal cells, including the retinal ganglion cell layer, inner plexiform layer, inner nuclear layer, and photoreceptor outer segments in both nondiabetic and diabetic retinopathy specimens. Strikingly, we observed significantly more ACE2 positive vessels in the diabetic retinopathy specimens. By contrast, in another end-stage organ affected by diabetes, the kidney, ACE2 in nondiabetic and diabetic nephropathy showed apical expression of ACE2 tubular epithelial cells, but no endothelial expression in glomerular or peritubular capillaries. Western blot analysis of protein lysates from HRECs and HRPCs confirmed expression of ACE2. TMPRSS2 expression was present in multiple retinal neuronal cells, vascular and perivascular cells, and Müller glia. CONCLUSIONS.Together, these results indicate that retina expresses ACE2 and TMPRSS2. Moreover, there are increased vascular ACE2 expression in diabetic retinopathy retinas.

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“…One demonstrated abnormalities of ACE2 and other RAS proteins in blood in people with T2D, but no change in these proteins following rapid improvement of glycemic control using insulin (13). Another showed increased expression of ACE2 in the liver in older age and in the presence of hepatic steatosis and diabetes, all factors associated with risk of progression to severe illness in COVID-19 (14). These clues support further efforts to determine the role of medications affecting RAS activity in patients with diabetes and COVID-19.…”

mentioning

confidence: 99%

Diabetes and COVID-19: Moving From News to Knowledge and a Glucose Hypothesis

Riddle

2020

Diabetes Care

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Increased Hepatic ACE2 Expression in NAFL and Diabetes—A Risk for COVID-19 Patients?

Cited by 28 publications

References 5 publications

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes—Implications for Retinopathy

Diabetes and COVID-19: Moving From News to Knowledge and a Glucose Hypothesis

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