The renin–angiotensin–aldosterone-system in sepsis and its clinical modulation with exogenous angiotensin II

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: Nov. 26, 2024

Abstract Dysregulation of the renin–angiotensin–aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with likely significant contribution to organ failure patient outcomes. A better understanding pathophysiology intricacies RAAS septic shock has led use exogenous angiotensin II as new therapeutic agent. In this review, we report multinational multi-disciplinary expert panel discussion on role implications modulation II. The proposed guidance regarding selection treatment options which should trigger further research.

Language: Английский

---

Removal of Soluble ACE2 in VeroE6 Cells by 17β-Estradiol Reduces SARS-CoV-2 Infectivity

Biological and Pharmaceutical Bulletin, Journal Year: 2023, Volume and Issue: 46(12), P. 1842 - 1845

Published: Oct. 20, 2023

Women are less susceptible than men to coronavirus disease 2019 (COVID-19), which might be due the female steroid hormone 17β-estradiol. We hypothesized that 17β-estradiol removes soluble portion of angiotensin-converting enzyme 2 (sACE2) severe acute respiratory syndrome (SARS-CoV-2) binds in host cells and sACE2 then virus, thereby reducing infectivity. In present study, VeroE6/serine protease transmembrane protein (TMPRSS2) were infected with pseudo SARS-CoV-2 viruses used as our model system. This infectivity was reduced by application After applying VeroE6/TMPRSS2 cells, we a sandwich enzyme-linked immunosorbent assay (ELISA) measure concentration culture medium. Our findings revealed from cells. Furthermore, incubated medium ACE2 collected 17β-estradiol-treated measured an ultrasensitive ELISA using anti-spike antibodies. The amount spike proteins decreased according applied. These results clearly demonstrated ACE2, removed bound SARS-CoV-2, COVID-19

Language: Английский

---

Degradation of the α-Carboxyl Terminus 11 Peptide: In Vivo and Ex Vivo Impacts of Time, Temperature, Inhibitors, and Gender in Rat

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(5), P. 1624 - 1636

Published: April 22, 2024

In previous research, a synthetic α-carboxyl terminus 1 (αCT1) peptide derived from connexin 43 (Cx43) and its variant (αCT11) showed beneficial effects in an ex vivo ischemia–reperfusion (I/R) heart injury model mouse. mouse of cryo-induced ventricular injury, αCT1 released adhesive cardiac patches reduced Cx43 remodeling arrhythmias, as well maintained conduction. Whether intravenous injection or αCT11 produces similar outcomes has not been investigated. Given the possibility degradation plasma, this study utilized I/R blood plasma models to examine factors that may limit therapeutic potential therapeutics vivo. Following tail vein administration (100 μM) blood, no effect on infarct size was observed adult rat hearts day (D1) 28 (D28) after (p > 0.05). There also difference echocardiographic ejection fraction (EF%) between control groups Surprisingly, collected these rats undetectable within ∼10 min injection. To investigate modulate directly added isolated normal without levels were measured under different experimental conditions. Consistent with observations, significant occurred 10 at 22 37 °C nearly by 30 min. These responses addition protease/phosphatase (PTase/PPTase) inhibitors plasma. Interestingly, differences noted male female rats. We conclude fast is likely reason inhibition shielding PTase/PPTase activity be strategy will assist viability therapeutics.

Language: Английский

---

Sex differences in coronavirus disease 2019 myocarditis

Current Opinion in Physiology, Journal Year: 2023, Volume and Issue: 35, P. 100704 - 100704

Published: July 21, 2023

Myocarditis is frequently caused by viral infections, but animal models that closely resemble human disease suggest virus-triggered autoimmune the most likely cause of myocarditis. a rare condition occurs primarily in men under age 50. The incidence myocarditis rose at least 15x during COVID-19 pandemic from 1-10 to 150-400 cases/100,000 individuals, with cases occurring vaccination was also associated young 50 years an as high individuals reported for some mRNA vaccines. Sex differences immune response are virtually identical mechanisms known drive sex pre-COVID based on clinical studies and models. many similarities between vaccine-associated non-COVID common disease.

Language: Английский

---

Association of Renin–Angiotensin Pathway Gene Polymorphisms with COVID-19 Susceptibility and Severity in Moroccans: A Case–Control Study

Biochemical Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Language: Английский

---

Factores genéticos asociados a long COVID

Medicina de Familia SEMERGEN, Journal Year: 2024, Volume and Issue: 50(2), P. 102187 - 102187

Published: Jan. 15, 2024

---

Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 7, 2022

Abstract Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating effects these factors. Recent evidence shows patient-specific alterations RAS homeostasis concentrations with premorbidity expression level angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting suggests decreases, increases, or no changes peptides after SARS-CoV-2 infection. In addition, detailed mechanisms connecting conditions before infection to infection-induced still unknown. Here, multiscale computational model was developed quantify systemic contribution Three submodels were connected—an agent-based for in-host response tissue, dynamics model, fibrosis investigate patient-group-specific alteration collagen deposition lung. results indicated cell death due inflammatory as major contributor reduction ACE ACE2. contrast, there ACE2 viral-bound internalization explained possible previously published studies. Simulated consistent reported peptide values SARS-CoV-2-negative SARS-CoV-2-positive patients. decreased all virtual patient groups aging both sexes. large variations magnitude observed between male female patients older middle-aged groups. also affected showed feedback signaling renin could restore ANGI concentration but failed downstream ANGI. age significantly altered led slight depending on sex. This may find further applications calibrations tissue models acute chronic diseases develop personalized treatments.

Language: Английский

---

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur

Circulation Research, Journal Year: 2023, Volume and Issue: 132(10), P. 1255 - 1258

Published: May 11, 2023

Language: Английский

---