The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19

Mendes, Gabriel Moreira de Mello; Nascimento, Israel Júnior Borges do; Marazzi-Diniz, Paulo Hs; Silveira, Izabela B Da; Itaborahy, Matheus F; Viana, Luiz E; Silva, Filipe A; Santana, Monique Freire; Pinto, Rebecca Aa; Dutra, Bruna Guimarães; Lacerda, Marcus Vinícius Guimarães; Araujo, Stanley A; Wanderley, David Campos; Vidigal, Paula Vt; Diniz, Paulo Hc; Verano‐Braga, Thiago; Santos, Robson A; Leite, M. Fátima

doi:10.3389/fphys.2022.1080837

“…Mendes et al using LC-MS/MS reported higher levels of Brad 1−8 alongside lower Brad levels in COVID-19 patient plasma compared to healthy controls. 35 In bronchoalveolar lavage fluids obtained from COVID-19 patients, Brad 1−8 and Brad 1−7 were reportedly increased with decreased Brad concentration using ELISA. 3 Our results are consistent with literature reports that dysregulation of the RAS−KKS may be responsible for symptoms experienced by COVID patients, supporting the move to therapeutically target these systems.…”

Section: ■ Results and Discussionmentioning

confidence: 95%

“…Also, severe disease conditions are characterized by difficulty in breathing, which may be related to enhanced production of Brad as well as other factors. Mendes et al using LC-MS/MS reported higher levels of Brad 1–8 alongside lower Brad levels in COVID-19 patient plasma compared to healthy controls . In bronchoalveolar lavage fluids obtained from COVID-19 patients, Brad 1–8 and Brad 1–7 were reportedly increased with decreased Brad concentration using ELISA .…”

Section: Results and Discussionmentioning

confidence: 98%

Levels of Angiotensin and Kinin Metabolite Peptides Related to COVID-19 Severity

Ahiadu,

Grunbaum,

Rozza

et al. 2023

ACS Pharmacol. Transl. Sci.

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In addition to crucial roles in normal human biology, peptide metabolites of the renin−angiotensin (RAS) and kallikrein−kinin systems (KKS) have been reported to be altered in COVID-19 patients. Here, we evaluate new data on RAS and KKS peptides in COVID-19 patient serum obtained from a recently developed, fully validated, and optimized stable isotope labeling LC-MS peptide assay. We found that the RAS peptides angiotensin (ANG) 1, 2, 1−5, and 1−7 were downregulated compared to COVID-free surrogate controls, while the KKS peptides Brad, Brad 1−8, and Brad 1−7 were upregulated. This paper focuses on uncovering the possible diagnostic value of these peptides using receiver operating characteristic (ROC) analyses of these data. ROC plots confirmed that all of the analyte peptides in 80 serum samples from COVID-19 patients were significantly altered from "normal" values of the control samples. The best diagnostic sensitivities and selectivities for COVID vs no COVID were found in ROC plots for Brad and Brad 1−7 (both 99% sensitivity, 100% selectivity). We then analyzed levels of all the peptides grouped according to preassigned values of the World Health Organization (WHO) COVID-19 Severity Index. ROC plots differentiated patients with a high WHO severity index from those with a low WHO severity index with moderate success, with BRAD (73% sensitivity, 79% selectivity) and Ang 1−7 (75% sensitivity, 65% selectivity) giving the best diagnostic performance. Results suggest the possible diagnostic value of these peptides as biomarkers to help identify moderate and serious COVID-19 cases at relatively early stages.

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“…Perhaps lower pulmonary ACE2 is Covid 19 protective, but the downregulated ACE2 may be associated with higher levels of des-Arg9-bradykinin (see figure 5). Des-arg-BKN appears to be a prominent kinin in Covid-19 75 .…”

Section: Autoimmunity In Femalesmentioning

confidence: 94%

LC, POTS, and ME/CFS: Lifting the Fog

Chambers¹

2023

Preprint

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These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

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“…Perhaps lower pulmonary ACE2 is Covid 19 protective, but the downregulated ACE2 may be associated with higher levels of des-Arg9-bradykinin (see figure 5). Des-arg-BKN appears to be a prominent kinin in Covid-19 73 .…”

Section: Autoimmunity In Femalesmentioning

confidence: 94%

Long Covid, POTS, and ME/CFS: Lifting the Fog

Chambers¹

2023

Preprint

0

View full text Add to dashboard Cite

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

show abstract

The des-Arg9-bradykinin/B1R axis: Hepatic damage in COVID-19

Cited by 13 publications

References 52 publications

Levels of Angiotensin and Kinin Metabolite Peptides Related to COVID-19 Severity

Levels of Angiotensin and Kinin Metabolite Peptides Related to COVID-19 Severity

LC, POTS, and ME/CFS: Lifting the Fog

Long Covid, POTS, and ME/CFS: Lifting the Fog

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