Neutrophil-Derived Myeloperoxidase and Hypochlorous Acid Critically Contribute to 20-Hydroxyeicosatetraenoic Acid Increases that Drive Postischemic Angiogenesis

Azcona, Juan A.; Tang, Samantha; Berry, Elizabeth; Zhang, Frank; Garvey, Radha; Falck, John R.; Schwartzman, Michal Laniado; Yi, Tao; Jeitner, Thomas M.; Guo, Austin M.

doi:10.1124/jpet.121.001036

Cited by 4 publications

(4 citation statements)

References 114 publications

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“…The evidence for heterogenous functions of neutrophils in disease stems partially from their discovered roles in neuronal and angiogenic repair in both spinal cord and optic nerve injury demonstrating direct and indirect protection [26, 27, 47, 50, 51]. These functions discovered in non-infection instances may be applicable to the demonstrated evidence of damaged neurons observed during chronic Toxoplasma infection [6, 7, 52].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, aged neutrophils have upregulated transcription of the effector genes Bmf and Pdgfb and also Vegfa, and Kdr, noted for their roles in tissue repair. The overlap of these seemingly contradictory functions is steadily increasing with the recognition that the production of NETs and peroxidases are also required for tissue repair as well as effector mechanisms against pathogens [27,46,50]. This underpins the concept of innate immune cells being as critical to tissue homeostasis as they are in initiating immune responses and may pinpoint neutrophil flexibility as important not only in Toxoplasma infection but also in all models of CNS disease.…”

Section: Neuronal Regeneration Attempts During Chronic Infection Are ...mentioning

confidence: 99%

“…This underpins the concept of innate immune cells being as critical to tissue homeostasis as they are in initiating immune responses and may pinpoint neutrophil flexibility as important not only in Toxoplasma infection but also in all models of CNS disease. The evidence for heterogenous functions of neutrophils in disease stems partially from their discovered roles in neuronal and angiogenic repair in both spinal cord and optic nerve injury demonstrating direct and indirect protection [26,27,47,50,51]. These functions discovered in non-infection instances may be applicable to the demonstrated evidence of damaged neurons observed during chronic Toxoplasma infection [6,7,52].…”

Section: Neuronal Regeneration Attempts During Chronic Infection Are ...mentioning

confidence: 99%

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Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Bergersen

Kavvathas

David

et al. 2022

Preprint

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Infection with the protozoan parasite Toxoplasma gondii leads to the formation of lifelong cysts in neurons of the brain that can have devastating consequences in the immunocompromised. However, despite the establishment of a chronic inflammatory state and infection-induced neurological changes, there are limited signs of clinical neuropathology resulting in an asymptomatic infection in the immunocompetent. This suggests the work of neuroprotective mechanisms to prevent clinical manifestations of disease. However, such sources of neuroprotection during infection remain largely unknown. This study identifies a population of neutrophils chronically present in the brain during Toxoplasma infection that express the neuroprotective molecules NRG-1, ErbB4, and MSR1. Further phenotyping of this population via flow cytometry and singe-cell RNA sequencing reveals two distinct subsets of neutrophils based on age that display functional heterogeneity. This includes cells transcriptionally prepared to function both as anti-parasitic effector cells and in a more alternative protective manner. Chronic depletion of neutrophils results in increased parasite burden and infection-induced vascular pathology. Lack of neutrophils during chronic infection also deleteriously affects neuronal regeneration and repair mechanisms. In conclusion, this work identifies and demonstrates a functionally diverse chronic neutrophil population that plays a dynamic role in controlling infection outcome in the CNS by balancing classical responses with neuroprotective functions.

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Section: Discussionmentioning

confidence: 99%

Section: Neuronal Regeneration Attempts During Chronic Infection Are ...mentioning

confidence: 99%

Section: Neuronal Regeneration Attempts During Chronic Infection Are ...mentioning

confidence: 99%

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Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Bergersen

Kavvathas

David

et al. 2022

Preprint

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“…A recent in vivo study showed that neutrophil-derived myeloperoxidase (MPO) activates proteins that drive postischemic angiogenesis [45].…”

Section: Immune and In Responsementioning

confidence: 99%

Impact of cardiac shock wave therapy on the dynamics of biomarkers: results of proteomic analysis

Burneikaitė

Jasiūnas

Shkolnik

et al. 2022

Preprint

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Background: Cardiac shock-wave therapy (CSWT) is a non-invasive treatment based on low-frequency ultrasound waves that stimulate angiogenesis. Current data on the effects of revascularization procedures on angiogenesis biomarkers are limited. In this study, we aimed to characterize the serum protein profiles of patients with coronary artery disease after CSWT treatment in relation to changes in exercise and imaging parameters. Methods: The study population included 10 patients from a prospective, randomized, triple-blind, sham-procedure controlled study (NCT02339454), who received CSWT and had demonstrated improvement in myocardial perfusion and/or contractility at 6 months follow-up The blood samples were collected at baseline, after the last treatment procedure (9th treatment week), at 6-month follow-up and stored at −80°C until analysis. The cardiovascular-related proteins (n=92) were measured using the Olink Proseek Multiplex Cardiovascular III panel (Olink, Uppsala, Sweden). Results: The median age was 65.5 years, and 7 patients were males. A total of 20 biomarkers showed significant changes from baseline to 9th week and 6 months follow-up (p<0.05). We identified 28 proteins that showed clear association with an increase in exercise tolerance and improvement in myocardial contractility or perfusion after CSWT. Using a volcano plot and results from the paired Mann-Whitney U test at confidence level of 0.95, we identified 3 proteins (PON3, TR-AP, CD163) with elevated values corresponding to increase in exercise duration (p<0.05) and 2 proteins (CPA1, COL1A1) related to improved myocardial contractility (p<0.05). A pathway analysis including 28 proteins suggested that these biomarkers were related to immune and inflammatory response, cell adhesion, tissue remodeling, proteolysis and catabolic processes. Conclusions: This study demonstrates the association of an increase in protein levels with an improvement in exercise duration and contractile function. Proteomic analysis suggests that CSWT exerts biological effects including immune and inflammation response, cell adhesion and tissue remodeling, all of which may mediate angiogenesis. Trial registration: Clinicaltrials.gov (NCT02339454).

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20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond

Pascale¹,

Wolf²,

Kadish³

et al. 2023

Advances in Pharmacology

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Neutrophil-Derived Myeloperoxidase and Hypochlorous Acid Critically Contribute to 20-Hydroxyeicosatetraenoic Acid Increases that Drive Postischemic Angiogenesis

Cited by 4 publications

References 114 publications

Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection

Impact of cardiac shock wave therapy on the dynamics of biomarkers: results of proteomic analysis

20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond

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