A5040284232- Atherosclerosis and Cardiovascular Diseases
- Sodium Intake and Health
- Nitric Oxide and Endothelin Effects
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Systemic Lupus Erythematosus Research
- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Celiac Disease Research and Management
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Monoclonal and Polyclonal Antibodies Research
- Antioxidant Activity and Oxidative Stress
- Ubiquitin and proteasome pathways
Vanderbilt University Medical Center
2022-2024
Vanderbilt University
2023
Salt sensitivity of blood pressure is an independent predictor cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases risk unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial channel EnaC (epithelial channel) leads to formation IsoLGs (isolevuglandins) release proinflammatory cytokines activate T modulate salt-sensitive hypertension. In current study, we hypothesized ENaC-dependent APCs...
BACKGROUND: Neutrophil extracellular traps (NETs) are composed of DNA, enzymes, and citrullinated histones that expelled by neutrophils in the process NETosis. NETs accumulate aorta kidneys hypertension. PAD4 (protein-arginine deiminase-4) is a calcium-dependent enzyme essential for TRPV4 (transient receptor potential cation channel subfamily V member 4) mechanosensitive calcium expressed neutrophils. Thus, we hypothesize NETosis contributes to hypertension via NET-mediated endothelial cell...
We describe a mechanism responsible for systemic lupus erythematosus (SLE). In humans with SLE and in 2 murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) monocytes dendritic cells. found that antibodies formed against isoLG adducts both SLE-prone mice SLE. addition, ligation the transcription factor PU.1 at critical DNA binding site markedly reduced all C1q subunits. Treatment specific scavenger 2-hydroxybenzylamine (2-HOBA) ameliorated parameters...
Hypertension is characterized by CD8
IsoLGs (isolevuglandins) are electrophilic products of lipid peroxidation formed in the presence reactive oxygen species. contribute to hypertension by an unknown mechanism. Studies have shown that species production drives formation neutrophil extracellular traps (NETs) and NETs accumulate within aorta kidneys patients with hypertension. The purpose this study was determine role isoLGs migration NET (NETosis) hypertension.Mice were treated Ang II (angiotensin II) specific isoLG scavenger...
Isolevuglandins (isoLGs) are lipid aldehydes that form in the presence of reactive oxygen species (ROS) and drive immune activation. We found isoLG-adducts presented within context major histocompatibility complexes (MHC-I) by an immunoproteasome dependent mechanism. Pharmacologic inhibition LMP7, chymotrypsin subunit immunoproteasome, attenuates hypertension tissue inflammation angiotensin II (Ang II) model hypertension. Genetic loss function all subunits or conditional deletion LMP7...
Objective Hypertension is frequent in patients with systemic lupus erythematosus (SLE) and a major contributor to increased cardiovascular risk. Isolevuglandins (IsoLGs) are downstream products of oxidative stress that drive hypertension SLE disease activity animal models. Antibodies IsoLGs (anti-IsoLGs) present human associated activity, but it not known if concentrations higher compared control subjects or they blood pressure (BP). Methods We measured serum anti-IsoLG IgG antibody by...
Background: Isolevuglandins (isoLGs) are products of lipid peroxidation that formed in the presence reactive oxygen species. IsoLGs increased circulating CD14 + monocytes patients with hypertension and contribute to inflammatory activation. When adducted histones, isoLGs prevent nucleosome assembly. Moreover, induce disassembly pre-formed nucleosomes. can be induced cell culture tert-butyl hydroperoxide (tBHP) efficiently scavenged by ethyl-2-hydroxybenzylamine (Et-2HOBA). We hypothesized...
Background: Neutrophils play a crucial role in the innate immune response, part by release of neutrophil extracellular traps (NETs), which consist decondensed chromatin and proteins including citrullinated histone 3 (H3-Cit). The process NETosis involves disassociation DNA from nucleosome catalyzed enzyme peptidyl arginine deiminase 4 (PAD4). TRPV4 is mechanosensitive calcium channel expressed neutrophils. Studies human subjects rodent models have described accumulation NETs renal vascular...