Autoantibodies to ACE2 and immune molecules are associated with COVID-19 disease severity

Communications Medicine, Journal Year: 2024, Volume and Issue: 4(1)

Published: March 15, 2024

Abstract Background Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term manifestations. The mechanisms of this variable immune activation are poorly defined. One feature increased is elevated levels proinflammatory cytokines chemokines. Autoantibodies targeting factors such as cytokines, well the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after infection. ACE2 could interfere with normal regulation inflammation, COVID-19, complications. Methods Here, we deeply profiled features ACE2, cytokine, chemokine autoantibodies in samples from patients recovering COVID-19. We measured immunoglobulin subclasses (IgG, IgA, IgM) peripheral blood against 23 other molecules. then utilized an peptide microarray map linear epitopes targeted autoantibodies. Results demonstrate that autoantibody individuals COVID-19 compared those mild or no prior identify near catalytic domain these antibodies. Levels serve determinants severity, represent a natural immunoregulatory mechanism response Conclusions These results increase factors. associated severity.

Language: Английский

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Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment

Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1320 - 1337

Published: May 11, 2023

The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause death and potentially contributed to a decline life expectancy United States. severe acute respiratory syndrome-related coronavirus-2 binds surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) tissue infection viral replication. ACE2 is important enzymatic component renin-angiotensin system (RAS) expressed lung other organs. regulates levels peptide hormones Ang II Ang-(1–7), which have distinct opposing actions one another, as well cardiovascular peptides. A potential consequence reduced activity by internalization viral-ACE2 complex subsequent activation RAS (higher ratio II:Ang-[1–7]) may exacerbate inflammatory events COVID-19 patients possibly contribute effects long COVID-19. Moreover, present with array autoantibodies various components including II, ACE2, AT 1 Mas receptors. Greater severity also evident male patients, reflect underlying sex differences regulation functional arms RAS. review provides critical evaluation evidence for activated subjects whether this contributes greater males compared females.

Language: Английский

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S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 204 - 204

Published: Jan. 17, 2023

Since the spread of deadly virus SARS-CoV-2 in late 2019, researchers have restlessly sought to unravel how enters host cells. Some proteins on each side interaction between and cells are involved as major contributors this process: (1) nano-machine spike protein behalf virus, (2) angiotensin converting enzyme II, mono-carboxypeptidase key component renin system cell, (3) some proteases exploited by SARS-CoV-2. In review, complex process entrance into with contribution well sequential conformational changes tending increase probability complexification latter receptor cells, discussed. Moreover, release catalytic ectodomain II its soluble form extracellular space positive or negative impact infectivity considered.

Language: Английский

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Immune system-related soluble mediators and COVID-19: basic mechanisms and clinical perspectives

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Aug. 29, 2022

Abstract During SARS-CoV-2 infection, an effective immune response provides the first line of defense; however, excessive inflammatory innate immunity and impaired adaptive may harm tissues. Soluble mediators are involved in dynamic interaction ligands with membrane-bound receptors to maintain restore health after pathological events. In some cases, dysregulation their expression can lead disease pathology. this literature review, we described current knowledge basic features soluble during infections highlighted contribution severity mortality.

Language: Английский

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Clinical studies in Myxomatous Mitral Valve Disease dogs: most prescribed ACEI inhibits ACE2 enzyme activity and ARB increases AngII pool in plasma

Hypertension Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract The hypertension patient population has doubled since 1990, affecting 1.3 billion globally and >75% live in low-and middle-income countries. Angiotensin Converting Enzyme Inhibitors (ACEI) Receptor Blockers (ARB) are the most prescribed drugs (>160 million times US), but mortality increased >30% 1990s globally. Clinical relevance of Myxomatous Mitral Valve Disease (MMVD) is directly linked to WHO group 2 pulmonary hypertension, with no disease specific therapies. Therefore, MMVD pet dogs elevated systolic blood pressure treated ACEI/ARB, were supplemented oral ACE2 enzyme Angiotensin1-7 (Ang1-7) bioencapsulated plant cells. ACE2/Ang1-7 was well tolerated by healthy adverse events sACE2 activity 670–755% ARB (Telmisartan) than ACEI (Enalapril) background therapy. In vitro rhACE2 inhibited >90% ACEIs enalapril/benazeprilat at higher doses lisinopril much lower doses. Membrane evaluated exosomes 43-fold this also 211% ACEI, when compared ARB. Background treatment reduced Ang-II pool 11-20-fold proportionately decreased abundance Ang1-7 + Ang1-5 peptides. contrast, 160–260%. Systolic regulated better despite very high levels. This first report on evaluation metabolic pools RAS pathway identifies surprising interactions between ACEI/ARB/ACE2 significant changes key molecular dynamics. Affordable biologics developed cells may offer potential new options for hypertension.

Language: Английский

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The Renin–Angiotensin System (RAS) in COVID-19 Disease: Where We Are 3 Years after the Beginning of the Pandemic

Microorganisms, Journal Year: 2024, Volume and Issue: 12(3), P. 583 - 583

Published: March 14, 2024

The RAS is a hormonal system playing pivotal role in the control of blood pressure and electrolyte homeostasis, alteration which associated with different pathologies, including acute respiratory distress syndrome (ARDS). As such, it not surprising that number studies have attempted to elucidate balance renin–angiotensin (RAS) COVID-19. In this review article, we will describe evidence collected regarding two main enzymes (i.e., ACE ACE2) their principal molecular products AngII Ang1-7) SARS-CoV-2 infection, overarching goal drawing conclusions on possible as clinical markers association disease severity, progression, outcome. Moreover, bring into picture new experimental data systemic activity ACE2 well concentration Ang1-7 cohort 47 COVID-19 patients hospitalized at IRCCS Sacro Cuore-Don Calabria Hospital (Negrar, Italy) between March April 2020. Finally, discuss possibility considering pathway marker for

Language: Английский

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Ursodeoxycholic acid does not reduce SARS-CoV-2 infection in newly allogeneic hematopoietic stem cell transplantation recipients: a prospective NICHE cohort

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: March 5, 2024

Introduction Retrospective studies have suggested that Ursodeoxycholic Acid (UDCA) provide a protective effect against SARS-CoV-2 infection, particularly in patients with liver disease. However, it is uncertain whether this finding can be extended to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Therefore, we aim examine potential of UDCA infection recently received allo-HSCT patients. Methods During initial Omicron variant wave China (December 2022 February 2023), conducted prospective observational study involving 91 hospitalized who had undergone within previous 6 months as part National Longitudinal Cohort Hematological Diseases (NICHE). Throughout hospitalization, continuously monitored status COVID-19 using PCR kits or Antigen Rapid Tests. Results Among these patients, 67.0% (n = 61) were confirmed contracted infection. For 52 evaluated, 23.1% experienced severe critical clinical course. There was no difference rate severity between group and non-UDCA group. We found only transplanted 3 ago demonstrated higher risk compared those (Odds Ratio [OR]: 3.241, 95% Confidence Interval [CI]: 1.287-8.814, P 0.016). But other factors, such administration UDCA, showed difference. Notably, age ≥38 years old remained an independent factor for course (OR: 3.664, CI: 1.129-13.007, 0.035). Conclusion The effectiveness protecting newly recipients remains unconfirmed. Presently, most effective strategy appears minimizing exposure SARS-CoV-2. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT04645199 , identifier NCT04645199.

Language: Английский

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Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19

Open Medicine, Journal Year: 2023, Volume and Issue: 18(1)

Published: Jan. 1, 2023

It is predictable that the renin-angiotensin-aldosterone and kinin-kallikrein systems are dysregulated in COVID-19 (COV) patients because SARS-CoV-2 requires ACE2 to cause an infection. This study aimed assess serum levels of des-arg(9)-bradykinin (DABK) angiotensin 1-7 (ang-(1-7)) with COV who had above-mentioned cardiovascular disease risk factors. In a cross-sectional study, 69 were selected among referred main referral center for these patients, Kerman, Iran, 73 matched control (non-COV) individuals participated KERCARD cohort study. Serum DABK ang-(1-7) measured by ELISA groups CTL (healthy), HTN, DM, OB, COV, + OB. Ang-(1-7) lower HTN group compared group. higher OB DM subjects their corresponding The related respectively. According findings, we can infer increase production those factors diabetes, obesity, hypertension or decrease may contribute adverse outcomes

Language: Английский

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Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation

Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(3), P. 101301 - 101301

Published: July 19, 2024

Language: Английский

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Evaluation of Biologics ACE2/Ang(1–7) Encapsulated in Plant Cells for FDA Approval: Safety and Toxicology Studies

Pharmaceutics, Journal Year: 2024, Volume and Issue: 17(1), P. 12 - 12

Published: Dec. 25, 2024

Background/Objectives: For several decades, protein drugs (biologics) made in cell cultures have been delivered as sterile injections, decreasing their affordability and patient preference. Angiotensin Converting Enzyme 2 (ACE2) gum is the first engineered human blood expressed plant cells approved by FDA without need for purification a cold-chain noninvasive drug delivery. This biologic currently being evaluated clinical studies to debulk SARS-CoV-2 oral cavity reduce coronavirus infection/transmission (NCT00543318). Methods: Chemistry, manufacturing, control (CMC) ACE2/Ang(1-7) substances (DSs) ACE2 product (DP) were conducted following USP guidelines. GLP-compliant toxicology on Sprague Dawley rats (n = 120; 15/sex/group) four groups-placebo, low (1.6/1.0 mg), medium (3.2/2.0 high (8.3/5.0 mg) doses IP/kg/day. Oral gavage was performed twice daily 14 days (the dosing phase) followed recovery phase (35 days). Plasma samples 216) analyzed Ang(1-7) ELISA. Results: The stable at least up 78 weeks. study revealed dose-related delivery plasma increases AUC (56.6%) Cmax (52.9%) after 28 high-dose gavages (95% C.I.), although this quantitation excludes exogenously membrane-associated ACE2/Ang(1-7). Vital biomarkers organs not adversely affected despite 10-fold higher absorption tissues, demonstrating safety in-human trials of NOAEL observed 2.5-7.5-fold than that anticipated efficacious therapeutic dose humans treatment cardiopulmonary disorders, it 314-fold topical via chewing gum. Conclusions: report lays foundation regulatory process approval affordable bioencapsulated cells.

Language: Английский

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