Reactive oxygen species in endothelial signaling in COVID-19: Protective role of the novel peptide PIP-2.

Introduction: Recent research suggests that endothelial activation plays a role in coronavirus disease 2019 (COVID-19) pathogenesis by promoting a pro-inflammatory state. However, the mechanism by which the endothelium is activated in COVID-19 remains unclear.

Objective: To investigate the mechanism by which COVID-19 activates the pulmonary endothelium and drives pro-inflammatory phenotypes.

Pulmonary vascular inflammation with fatal coronavirus disease 2019 (COVID-19): possible role for the NLRP3 inflammasome.

Background: Pulmonary hyperinflammation is a key event with SARS-CoV-2 infection. Acute respiratory distress syndrome (ARDS) that often accompanies COVID-19 appears to have worse outcomes than ARDS from other causes. To date, numerous lung histological studies in cases of COVID-19 have shown extensive inflammation and injury, but the extent to which these are a COVID-19 specific, or are an ARDS and/or mechanical ventilation (MV) related phenomenon is not clear.

Acute e-cig inhalation impacts vascular health: a study in smoking naïve subjects.

This study was designed to investigate the acute effects of nonnicotinized e-cigarette (e-cig) aerosol inhalation in nonsmokers both in terms of blood-based markers of inflammation and oxidative stress and evaluate their association with hemodynamic-metabolic MRI parameters quantifying peripheral vascular reactivity, cerebrovascular reactivity, and aortic stiffness. Thirty-one healthy nonsmokers were subjected to two blood draws and two identical MRI protocols, each one before and after a standardized e-cig vaping session. After vaping, the serum levels of C-reactive protein, soluble intercellular adhesion molecule, and the danger signal machinery high-mobility group box 1 (HMGB1) and its downstream effector and the NLR family pyrin domain containing 3 (NLRP3) inflammasome (as monitored by its adaptor protein ASC) increased significantly relative to the respective baseline (prevaping) values.

Correction: Fisher, Aron B., et al. A Peptide Inhibitor of NADPH Oxidase (NOX2) Activation Markedly Decreases Mouse Lung Injury and Mortality Following Administration of Lipopolysaccharide (LPS). Int. J. Mol. Sci. 2019, 20, 2395.

The authors wish to make the following corrections to our previously published paper [1] [...

Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI.

Background Previous studies showed that nicotinized electronic cigarettes (hereafter, e-cigarettes) elicit systemic oxidative stress and inflammation. However, the effect of the aerosol alone on endothelial function is not fully understood. Purpose To quantify surrogate markers of endothelial function in nonsmokers after inhalation of aerosol from nicotine-free e-cigarettes.

Acute exposure to e-cigarettes causes inflammation and pulmonary endothelial oxidative stress in nonsmoking, healthy young subjects.

The effects of e-cigarette (e-cig) aerosol inhalation by nonsmokers have not been examined to date. The present study was designed to evaluate the acute response to aerosol inhalation of non-nicotinized e-cigarettes in terms of oxidative stress and indices of endothelial activation in human pulmonary microvascular endothelial cells (HPMVEC). Ten smoking-naïve healthy subjects (mean age ± SD = 28.

Peroxiredoxin6 in Endothelial Signaling.

Peroxiredoxins (Prdx) are a ubiquitous family of highly conserved antioxidant enzymes with a cysteine residue that participate in the reduction of peroxides. This family comprises members Prdx1⁻6, of which Peroxiredoxin 6 (Prdx6) is unique in that it is multifunctional with the ability to neutralize peroxides (peroxidase activity) and to produce reactive oxygen species (ROS) via its phospholipase (PLA₂) activity that drives assembly of NADPH oxidase (NOX2). From the crystal structure, a C47 residue is responsible for peroxidase activity while a catalytic triad (S32, H26, and D140) has been identified as the active site for its PLA₂ activity.

Nrf2-Mediated Antioxidant Defense and Peroxiredoxin 6 Are Linked to Biosynthesis of Palmitic Acid Ester of 9-Hydroxystearic Acid.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising antidiabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, quantitative trait locus mapping, and correlation analyses in rat BXH/HXB recombinant inbred strains, as well as response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs. Comprehensive analysis of WAT samples identified ∼160 regioisomers, documenting the complexity of this lipid class.

Anti-inflammatory effects on ischemia/reperfusion-injured lung transplants by the cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) inhibitor vildagliptin.

Objectives: We showed previously that stromal cell-derived factor 1 (SDF-1) is a substrate of cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) and exerts regenerative properties on acute lung ischemia-reperfusion injury on CD26/DPP4 inhibition. Here, we extend our studies to test whether an intermediate recovery of lung transplants from ischemia/reperfusion injury by CD26/DPP4 inhibition can be achieved for up to 14 days.

Methods: Syngeneic mouse lung transplantation (Tx) was performed in C57BL/6 and in CD26-/- mice by applying 18 hours of cold ischemia.

Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS).

Binding sites for interaction of peroxiredoxin 6 with surfactant protein A.

Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A2 (PLA2) activities. This protein participates in the degradation and remodeling of internalized dipalmitoylphosphatidylcholine (DPPC), the major phospholipid component of lung surfactant. We have shown previously that the PLA2 activity of Prdx6 is inhibited by the lung surfactant-associated protein called surfactant protein A (SP-A) through direct protein-protein interaction.

Inhibition of the phospholipase A2 activity of peroxiredoxin 6 prevents lung damage with exposure to hyperoxia.

Lung injury associated with hyperoxia reflects in part the secondary effects of pulmonary inflammation and the associated production of reactive oxygen species due to activation of NADPH oxidase, type 2 (NOX2). Activation of NOX2 requires the phospholipase A2 (PLA2) activity of peroxiredoxin 6 (Prdx6). Therefore, we evaluated whether blocking Prdx6 PLA2 activity using the inhibitor MJ33 would be protective in a mouse model of acute lung injury resulting from hyperoxic exposure.

Dextran and polymer polyethylene glycol (PEG) coating reduce both 5 and 30 nm iron oxide nanoparticle cytotoxicity in 2D and 3D cell culture.

Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured.

Cx43/beta-gal inhibits Cx43 transport in the Golgi apparatus.

A connexin construct consisting of bacterial beta-galactosidase fused to the C-terminus of connexin43 (Cx43/beta-gal) was used to examine Cx43 assembly in NIH 3T3 cells. Cx43/beta-gal is retained in a perinuclear compartment and inhibits Cx43 transport to the cell surface. The intracellular connexin pool trapped by Cx43/beta-gal was retained in a compartment that co-localized with a medial Golgi apparatus marker by immunofluorescence microscopy and that was readily disassembled by treatment with brefeldin A.