scholarly journals Why Is COVID-19 More Severe in Patients With Diabetes? The Role of Angiotensin-Converting Enzyme 2, Endothelial Dysfunction and the Immunoinflammatory System

2021 ◽  
Vol 7 ◽  
Author(s):  
Jacob Roberts ◽  
Antonia L. Pritchard ◽  
Andrew T. Treweeke ◽  
Adriano G. Rossi ◽  
Nicole Brace ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Inflammatory Responses ◽  
Severe Form ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Inflammatory Processes ◽  
Meta Analyses

Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.

scholarly journals Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2

2009 ◽  
Vol 83 (11) ◽  
pp. 5451-5465 ◽  
Author(s):  
Naoko Yoshikawa ◽  
Tomoki Yoshikawa ◽  
Terence Hill ◽  
Cheng Huang ◽  
Douglas M. Watts ◽  
...  
Keyword(s):  
T Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Viral Infection ◽  
Inflammatory Responses ◽  
Fatal Outcome ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Inflammatory Infiltrates ◽  
The Brain

ABSTRACT We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8+ T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.

scholarly journals Angiotensin-converting enzyme 2: a double-edged sword in COVID-19 patients with an increased risk of heart failure

2020 ◽  
Author(s):  
Iman Razeghian-Jahromi ◽  
Mohammad Javad Zibaeenezhad ◽  
Zhibing Lu ◽  
Elyaspour Zahra ◽  
Razmkhah Mahboobeh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk

scholarly journals Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37649 ◽  
Author(s):  
Fengxia Xiao ◽  
Swapnil Hiremath ◽  
Greg Knoll ◽  
Joseph Zimpelmann ◽  
Kajenny Srivaratharajah ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Transplant Patients ◽  
Patients With Diabetes ◽  
Renal Transplant Patients

scholarly journals Prerequisites for Improving the Anti-epidemic Regime in Medical Organizations in the Context of the COVID-19 Pandemic

2020 ◽  
Vol 3 (38) ◽  
pp. 17-20
Author(s):  
Assel Khassenova ◽  
◽  
Zaituna Khamidullina ◽  
Zhuldyz Danbayeva ◽  
Gulnoza Aldabekova ◽  
...  
Keyword(s):  
Health Care ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Contact Mode ◽  
Angiotensin Converting Enzyme 2 ◽  
Oral Transmission ◽  
Leading Role ◽  
Increased Risk ◽  
Rapid Spread ◽  
Mode Of Transmission

Abstract The pandemic of COVID-19 remained the central issue for public health due to the rapid spread and high contagiousness of the virus. In Kazakhstan, anti-epidemic measures developed and implemented came as sufficient prevention, which provides the prevention of airborne and contact mode of transmission. However, there are studies that indicated the existence of a fecal-oral mode of transmission due to the presence of angiotensin converting enzyme 2 (ACE2) on the surface of cells of the gastrointestinal tract. Health care workers are at a significantly increased risk of infection because they are in constant contact with potential sources of viral infection. The personnel of medical organizations play a leading role in the fight against the pandemic; the task of the health care system is to create conditions for maintaining and strengthening their health. Considering persisting risks, it is necessary to foresee possible routes of transmission of infection and strengthen the anti-epidemic measurements, taking into account the fecal-oral mode of transmission. Key words: COVID-19, anti-epidemic measures, nosocomial infection, fecal-oral transmission, angiotensin converting enzyme 2 (ACE2), Kazakhstan.

scholarly journals Emerging highlights from novel human coronavirus and angiotensin-converting enzyme 2: promising way to target brain vascular diseases

2020 ◽  
Vol 10 (4) ◽  
pp. 130-134
Author(s):  
Caroline Bozzetto Ambrosi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Treatment Strategies ◽  
Vascular Diseases ◽  
Human Cells ◽  
Converting Enzyme ◽  
Human Coronavirus ◽  
Angiotensin Converting Enzyme 2 ◽  
Increased Risk ◽  
Almost All ◽  
Open The Doors

A specific metallopeptidase called angiotensin-converting enzyme 2 (ACE2) has been identified as the modulating receptor on the surface of the endothelium and other human cells infected by the new coronavirus causing Severe Acute Respiratory Syndrome (SARS-CoV-2) and Human Coronavirus Disease 2019 (COVID -19). This modulation of the expression of ACE2 in human cells may be responsible for the production of pro-inflammatory response with the development of the state of the systemic response of the inflammatory system, hypercoagulability/stasis also an increased risk of both ischemic and hemorrhagic strokes. Therefore, like ACE2, despite being present in almost all human organs, its expression is variable and probably dependent on epigenetic polymorphism, then this is still to be better understood. However, this highlights the importance to understand its pathogenesis and open the doors for the development of future treatment strategies aimed at various diseases related to ACE2, mainly cerebral vascular diseases, and perhaps COVID-19 itself.

scholarly journals Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19

2020 ◽  
Author(s):  
Saba Al Heialy ◽  
Mahmood Hachim ◽  
Abiola Senok ◽  
Ahmad Abou Tayoun ◽  
Rifat Hamoudi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Pulmonary Inflammation ◽  
Lipid Synthesis ◽  
Lung Epithelial Cells ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Obesity And Diabetes ◽  
Increased Risk

AbstractThe ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene which is involved in regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs which negatively correlated with the expression of genes that code for sterol response element binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Together our results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

scholarly journals Lack of Association between Angiotensin Converting Enzyme I/D Polymorphism and Unexplained Recurrent Miscarriage in Saudi Arabia

2016 ◽  
Vol 35 (2) ◽  
pp. 166-174 ◽  
Author(s):  
Fatimah Basil Al-Mukaynizi ◽  
Afrah AlKhuriji ◽  
Zaineb Babay ◽  
Mohammad Addar ◽  
Sooad AlDaihan ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Recurrent Miscarriage ◽  
University Hospital ◽  
Control Group ◽  
Converting Enzyme ◽  
Chi Square ◽  
Ace Gene ◽  
Increased Risk ◽  
Unexplained Recurrent Miscarriage ◽  
Meta Analyses

Summary Background: An insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene has been associated with recurrent miscarriage (RM) in several populations. We initiated this study to determine the association, if any, between the I/D polymorphism of ACE gene and RM in Saudi females. Method: This study was conducted on 61 Saudi females suffering from RM (mean age: 34.1±6.2 years; range 15–45) attending clinics at King Khalid University Hospital, and 59 age matched females who had at least 2 children, as controls. Blood samples were drawn in EDTA tubes by venipuncture. DNA was extracted using the Puregene DNA purification kits. Insertion/Deletion (I/D) polymorphism of ACE gene was investigated by amplifying the genomic DNA by PCR using gene-specific primers. A single 190 bp or 490 bp band was obtained in the homozygous cases for the D allele or I allele, respectively, while the presence of both 190 and 490 bp bands indicated heterozygosity (ID). Statistical analysis: Deviation from Hardy-Weinberg equilibrium was determined (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl). A standard chi-square (χ2) test was used for comparing the genotype and allele frequencies in the two groups and Students‘t’ test and χ2 test were employed to compare values between the two groups. P<0.05 was considered statistically significant. Results: The frequencies of DD, ID, and II genotypes were 56.7%, 29.5% and 4.9%, respectively, in females with RM and 54.2%, 42.3% and 3.3% respectively in the control group, but the difference was not statistically significant. Conclusion: In some populations, meta-analyses showed an association between I/D polymorphism and RM risk, and the D allele was implicated as an increased risk factor for RM. However, this association was not apparent in the Saudi females.

scholarly journals Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2

2021 ◽  
Vol 12 ◽  
Author(s):  
Yaozhen Wang ◽  
Wenwen Fu ◽  
Yan Xue ◽  
Zeyuan Lu ◽  
Yuangeng Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Vascular Complications ◽  
Health Concern ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Anti Inflammatory ◽  
Ginsenoside Rc

Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.

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