Dataset Information

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

ABSTRACT: Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor. SARS-CoV-2 infection causes a reduction in ACE2 levels, leading to an imbalance in the renin-angiotensin system (RAS), and consequently, in blood pressure and systemic vascular resistance. ERAP1 and ERAP2 are two RAS regulators and key components of MHC class I antigen processing. Their polymorphisms have been associated with autoimmune and inflammatory conditions, hypertension, and cancer. Based on their involvement in the RAS, we believe that the dysfunctional status of ERAP1 and ERAP2 enzymes may exacerbate the effect of SARS-CoV-2 infection, aggravating the symptomatology and clinical outcome of the disease. In this review, we discuss this hypothesis.

SUBMITTER: D'Amico S

PROVIDER: S-EPMC7914632 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

D'Amico Silvia S Tempora Patrizia P Lucarini Valeria V Melaiu Ombretta O Gaspari Stefania S Algeri Mattia M Fruci Doriana D

International journal of molecular sciences 20210208 4

Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-Co ...[more]

PMID: 33567739

Similar Datasets

Project description:The coronavirus SARS-CoV-2 (COVID19) pandemic has pushed health workers to find creative solutions to a global shortage of personal protection equipment (PPE). 3D-printing technology is having an essential role during the pandemic providing solutions for this problem, for instance, modifying full-face snorkel masks or creating low-cost face shields to use as PPE (Ishack and Lipner, 2020 [1]). Otolaryngologists are at increased occupational risk to COVID19 infection due to the exposure to respiratory droplets and aerosols, especially during the routine nose and mouth examinations where coughing and sneezing happen regularly (Rna et al., 2017 [2]; Tysome and Bhutta, 2020 [3]). The use of a headlight is essential during these examinations. However, to our knowledge, none of the commercially available or 3D-printable face shields are compatible with a headlight. Hence, using a face shield and a headlight at the same time can be very uncomfortable and sometimes impossible. To solve this problem, we have designed a 3D-printable adapter for medical headlights, which can hold a transparent sheet to create a face shield as an effective barrier protection that can be used comfortably with the headlight. The adapter can be printed in different materials with the most commonly used nowadays being the cost-efficient PLA (Polylactic Acid) used for this prototype. The resulting piece weighs only 7 g and has an estimated cost of $0.15 USD. The transparent sheets, typically made from polyester and used for laser printing, can be purchased in any office material store with a standard price of 0.4 USD per unit. After use, the transparent sheet can be easily removed. We trialed the adapter in 7 different headlights. All of these headlights accommodated the printed blocks extremely well. The headlights were used in many different settings, including the ENT clinic, the operating room, the emergency room, the ENT ward and the COVID19 intensive care unit (ICU) for a two weeks period. All doctors using the headlight felt they were fully protected from respiratory droplets, blood, sputum and other fluids. The face shield with the headlight has been found very useful for treating epistaxis, changing tracheostomy cannulas and during routine nasal and oral examinations. The headlight face shield adapter was designed to solve a specific problem among the ENT community; however other specialist can find it useful as well. Nonetheless, manufacturers should take care of specifics problems like this and provide commercially available products to protect the ENT workforce in this new era.

Project description:Pre-eclampsia (PE) is a disorder of pregnancy, often leading to serious and fatal complications. Endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1/ERAP2) are present in the placenta. They are involved in processes regulating blood pressure, angiogenesis, cytokine receptor shedding, and immune recognition. Previous studies have associated both ERAP1/ERAP2 genetic variants with PE, although the underlying mechanisms remain unknown. Less is known about the roles for these enzymes in early placentation, which could be a contributory factor to PE. To ascertain whether ERAP1/ERAP2 change in PE and whether such a change is present before PE is clinically diagnosed, we analyzed mRNA and ERAP1/2 protein expression in the placenta in the early first trimester (8-14 weeks) and at delivery in normotensive or PE women (n = 12/group). Gene expression was analyzed using qPCR, and protein expression and localization were assessed by immunohistochemistry. Additionally, we profiled peripheral immune cells from normotensive and PE (n = 5/group) women for activation and expression of cytotoxic markers using flow cytometry to investigate a possible correlation with placental expression of ERAP1/2. Finally, we characterized the cytokines released from immune cells isolated from normotensive women and those with PE, stimulated ex vivo by JEG-3 trophoblast cells. The ERAP1 protein was significantly upregulated in first trimester placentae compared to placentae at delivery from both normotensive and PE women (p < 0.05): expression of placental ERAP1 protein was also relatively higher in normotensive than PE women. Although the protein expression of both ERAP1/ERAP2 was significantly lower in women with PE compared to normotensive controls (p < 0.05), ERAP2 protein expression remained unchanged in normotensive women at delivery compared to expression in the first trimester. Flow cytometry analysis revealed an increase in activation and cytotoxic natural killer (NK) cells in peripheral blood of PE compared to normotensive women. Intriguingly, there was a notable difference in cytokine release from the activated immune cells when further stimulated by trophoblast cells. The immune cells from PE released elevated expressions of interleukin (IL)-2, IL-4, and most notably, pro-inflammatory IL-13 and IL-17?, inflammatory cytokines tumor necrosis factor (TNF)-? and interferon (IFN)-?, and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to normal peripheral blood mononuclear cells (PBMCs). Taken together, these findings suggest that differential lymphocyte activation could be associated with altered ERAP1/ERAP2 expression.

Project description:BackgroundNovel coronavirus disease 2019 (COVID-19) has become a pandemic, and over 80 million cases and over 1.8 million deaths were reported in 2020. This highly contagious virus is spread primarily via respiratory droplets from face-to-face contact and contaminated surfaces as well as potential aerosol spread. Over half of transmissions occur from presymptomatic and asymptomatic carriers. Although several vaccines are currently available for emergency use, there are uncertainties regarding the duration of protection and the efficacy of preventing asymptomatic spread. Thus, personal protective health behaviour and measures against COVID-19 are still widely recommended after immunization. This study aimed to clarify the efficacy of these measures, and the results may provide valuable guidance to policymakers to educate the general public about how to reduce the individual-level risk of COVID-19 infection.MethodsThis case-control study enrolled 24 laboratory-confirmed COVID-19 patients from Centro Hospitalar Conde de São Januário (C.H.C.S.J.), which was the only hospital designated to manage COVID-19 patients in Macao SAR, China, and 1113 control participants who completed a 14-day mandatory quarantine in 12 designated hotels due to returning from high-risk countries between 17 March and 15 April 2020. A questionnaire was developed to extract demographic information, contact history, and personal health behaviour.ResultsParticipants primarily came from the United Kingdom (33.2%), followed by the United States (10.5%) and Portugal (10.2%). Independent factors for COVID-19 infection were having physical contact with confirmed/suspected COVID-19 patients (adjusted OR, 12.108 [95% CI, 3.380-43.376], P < 0.005), participating in high-risk gathering activities (adjusted OR, 1.129 [95% CI, 1.048-1.216], P < 0.005), handwashing after outdoor activity (adjusted OR, 0.021 [95% CI, 0.003-0.134], P < 0.005), handwashing before touching the mouth and nose area (adjusted OR, 0.303 [95% CI, 0.114-0.808], P < 0.05), and wearing a mask whenever outdoors (adjusted OR, 0.307 [95% CI, 0.109-0.867], P < 0.05). The daily count of handwashing remained similar between groups. Only 31.6% of participants had a sufficient 20-s handwashing duration.ConclusionsParticipating in high-risk gatherings, wearing a mask whenever outdoors, and practising hand hygiene at key times should be advocated to the public to mitigate COVID-19 infection.

Dataset Information

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

Publications

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets