A5018667400- Sodium Intake and Health
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Hormonal Regulation and Hypertension
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Blood Pressure and Hypertension Studies
- Apelin-related biomedical research
- GDF15 and Related Biomarkers
- Inflammatory mediators and NSAID effects
- Allergic Rhinitis and Sensitization
- Atherosclerosis and Cardiovascular Diseases
- Inhalation and Respiratory Drug Delivery
- Vitamin D Research Studies
- Pulmonary Hypertension Research and Treatments
- Respiratory viral infections research
- Neonatal Respiratory Health Research
- Adipokines, Inflammation, and Metabolic Diseases
- Urticaria and Related Conditions
- Renal Diseases and Glomerulopathies
- Diabetes Treatment and Management
- Inflammasome and immune disorders
- S100 Proteins and Annexins
- Caveolin-1 and cellular processes
- Computational Drug Discovery Methods
Indiana University – Purdue University Indianapolis
2023-2025
Indiana University Health
2024
Vanderbilt University Medical Center
2014-2023
Pulmonary and Allergy Associates
2020-2023
Indiana University School of Medicine
2023
University of Cincinnati
2023
Vanderbilt University
2013-2021
Mansoura University
2013-2016
Universidade Estadual de Campinas (UNICAMP)
2016
Cedars-Sinai Medical Center
2016
Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed experimental animals, we sought to determine whether human are activated We used a humanized mouse model which murine immune system is replaced by system. Angiotensin II increased systolic pressure 162 versus 116 mm Hg sham-treated animals. Flow cytometry thoracic lymph nodes, aorta, and kidney revealed infiltration leukocytes (CD45(+)) lymphocytes...
Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis hypertension. We sought to determine T-cell subtypes that contribute hypertension renal inflammation angiotensin II-induced Using receptor spectratyping examine usage, we demonstrated CD8(+) but not CD4(+) kidney exhibited altered transcript lengths Vβ3, 8.1, 17 families response Clonality was observed other organs. The caused by II CD4(-/-) MHCII(-/-) mice similar wild-type mice, whereas...
Angiotensin II–induced hypertension is associated with an increase in T-cell production of interleukin-17A (IL-17A). Recently, we reported that IL-17A −/− mice exhibit blunted hypertension, preserved natriuresis response to a saline challenge, and decreased renal sodium hydrogen exchanger 3 expression after 2 weeks angiotensin II infusion compared wild-type mice. In the current study, performed transporter profiling deficient or related isoform, IL-17F, 4 Ang infusion, time when blood...
Rationale: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis hypertension. Formation memory cells, which requires costimulatory molecule CD70 on antigen-presenting is cardinal feature immunity. Objective: To test hypothesis that immunologic contribute to blood pressure elevation renal dysfunction mediated by repeated hypertensive challenges. Methods Results: We imposed challenges using either N ω -nitro-L-arginine methyl ester...
The lymphocyte adaptor protein LNK (also known as SH2B3) is primarily expressed in hematopoietic and endothelial cells, where it functions a negative regulator of cytokine signaling cell proliferation. Single-nucleotide polymorphisms the gene encoding are associated with autoimmune cardiovascular disorders; however, not how contributes to hypertension. Here, we determined that loss exacerbates angiotensin II–induced (Ang II–induced) hypertension renal vascular dysfunction. At baseline,...
We previously showed that angiotensin II (Ang II) increases T cell production of IL-17A, and mice deficient in IL-17A have blunted hypertension attenuated renal vascular dysfunction. It was recently shown salt enhances from CD4+ cells via a serum- glucocorticoid-regulated kinase 1-dependent (SGK1-dependent) pathway. Thus, we tested the hypothesis SGK1 signaling promotes contributes to end-organ damage. show loss results hypertensive response Ang infusion by 25 mmHg. Importantly, inflammation...
To characterize the T cell subsets producing interleukin 17 (IL-17) isoforms A and F in hypertensive kidneys vessels determine whether inhibition of IL-17 signaling lowers blood pressure end-organ damage a mouse model hypertension.T derived cytokines play central role pathophysiology hypertension contribute to dysfunction. We previously showed that mice genetically deficient IL-17A exhibited blunted reduced renal vascular dysfunction response angiotensin II (Ang II) infusion. Monoclonal...
Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated by integrating GWAS whole mRNA expression profiles in 3,679 individuals, using network approaches. transcriptomic signatures at the single-gene and coexpression module levels were identified. Four modules as potentially causal based on genetic inference because expression-related...
Women have higher prevalence of asthma compared with men. In asthma, allergic airway inflammation is initiated by IL-33 signaling through ST2, leading to increased IL-4, IL-5, and IL-13 production eosinophil infiltration. Foxp3+ Tregs suppress ST2+ promote inflammation. Clinical studies showed that the androgen dehydroepiandrosterone (DHEA) reduced symptoms in patients, mouse receptor (AR) decreased Yet impact AR on lung remains unclear. Using AR-deficient Foxp3 fate-mapping mice, we...
Type 2 inflammatory diseases are common in cystic fibrosis (CF) including asthma, sinusitis, and allergic bronchopulmonary aspergillosis. CD4+ T helper (Th2) cells promote these through secretion of IL-4, IL-5, IL-13. Whether the transmembrane conductance regulator (CFTR), mutated protein CF, has a direct effect on Th2 development is unknown. Using murine models CFTR deficiency human cells, we show expressed Cftr transcript following activation. Loss cell expression increased cytokine...
Oxidative damage is implicated in atrial fibrillation (AF), but antioxidants are ineffective therapeutically. The authors tested the hypothesis that highly reactive lipid dicarbonyl metabolites, or isolevuglandins (IsoLGs), principal drivers of AF during hypertension. In a hypertensive murine model and stretched atriomyocytes, scavenger 2-hydroxybenzylamine (2-HOBA) prevented IsoLG adducts preamyloid oligomers (PAOs), susceptibility, whereas analog 4-hydroxybenzylamine (4-HOBA) had minimal...
Type 2 inflammation has been described in people with cystic fibrosis (CF). Whether loss of CFTR (cystic transmembrane conductance regulator) function contributes directly to a type inflammatory response not fully defined.
T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. follicular helper (Tfh) that interleukin 21 (IL21) promote germinal center (GC) cell responses leading to immunoglobulin (Ig) production. Here we investigate role of IL21 Tfh hypertension. In angiotensin (Ang) II-induced production increased, Il21-/- mice develop blunted attenuated vascular end-organ damage, decreased 17A (IL17A) interferon gamma Tfh-like GC...
In regions of the circulation where vessels are straight and unbranched, blood flow is laminar unidirectional. contrast, at sites curvature, branch points, distal to stenoses, becomes disturbed. Atherosclerosis preferentially develops in these disturbed flow. Current therapies for atherosclerosis systemic may not sufficiently target atheroprone regions. this study, we sought leverage alterations on luminal surface endothelial cells caused by nanocarrier targeting. vivo phage display was used...
Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach determine whether hypertensive individuals on conventional therapy exhibit altered monocyte gene expression profile and perform validation studies selected genes identify novel therapeutic targets for hypertension.Next generation RNA sequencing identified differentially expressed small discovery cohort normotensive individuals. Several these were further investigated association with...
The cyclooxygenase (COX) metabolic pathway regulates immune responses and inflammation. effect of the COX on innate pulmonary inflammation induced by protease-containing fungal allergens, such as Alternaria alternata, is not fully defined. In this study, we tested hypothesis that inhibition augments Alternaria-induced group 2 lymphoid cell (ILC2) IL-33 release. Mice were treated with inhibitors indomethacin, flurbiprofen, or vehicle challenged intranasally extract for four consecutive days...
Tregs restrain both the innate and adaptive immune systems to maintain homeostasis. Allergic airway inflammation, characterized by a Th2 response that results from breakdown of tolerance innocuous environmental antigens, is negatively regulated Tregs. We previously reported prostaglandin I2 (PGI2) promoted in models allergic inflammation; however, effect PGI2 on Treg function was not investigated. mice deficient receptor IP (IP KO) had impaired suppressive capabilities during inflammatory...