A5012435694- Hormonal Regulation and Hypertension
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Cardiac Fibrosis and Remodeling
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Inflammatory mediators and NSAID effects
- Synthesis of β-Lactam Compounds
- Stress Responses and Cortisol
- Eicosanoids and Hypertension Pharmacology
- Diet and metabolism studies
- Signaling Pathways in Disease
- Atherosclerosis and Cardiovascular Diseases
- Macrophage Migration Inhibitory Factor
- Biochemical Analysis and Sensing Techniques
- Cardiac Ischemia and Reperfusion
- Electrolyte and hormonal disorders
- Sodium Intake and Health
- IL-33, ST2, and ILC Pathways
- Curcumin's Biomedical Applications
- Cardiovascular Function and Risk Factors
- Coenzyme Q10 studies and effects
- Adrenal Hormones and Disorders
University of Michigan
2014-2025
Michigan United
2014
Laboratoire d’immunologie intégrative du cancer
2011
University of North Dakota
2009
Inappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, associated with increased inflammation and risk cardiovascular disease. MR antagonists are cardioprotective antiinflammatory in vivo, evidence suggests that they mediate these effects part by aldosterone-independent mechanisms. Here we have shown on myeloid cells necessary for efficient classical macrophage activation proinflammatory cytokines. Macrophages from mice lacking (referred...
Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A 2 formed by platelets AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas activity is preferentially blocked inhibitors called coxibs. COXs homodimers composed identical subunits, but we have shown that only one...
Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both and enzyme synthesizes it, aconitate decarboxylase 1 (Acod1, also known "immune-responsive gene 1"/IRG1) are upregulated during atherogenesis mice. Deletion Acod1 myeloid cells exacerbated inflammation atherosclerosis vivo resulted an elevated frequency specific subset M1-polarized proinflammatory macrophages atherosclerotic aorta....
mineralocorticoid receptor (MR) antagonists have protective effects in rodent models of ischemic stroke, but the cell type-specific actions these drugs are unknown. In present study, we examined contribution myeloid MR during focal cerebral ischemia using myeloid-specific knockout mice.myeloid-specific mice were subjected to transient (90 minutes) middle artery occlusion followed by 24 hours reperfusion (n=5 7 per group). Ischemic infarcts identified hematoxylin and eosin staining quantified...
Abstract Objective The intersection between immunology and metabolism contributes to the pathogenesis of obesity‐associated metabolic diseases as well molecular control inflammatory responses. metabolite itaconate cell‐permeable derivatives have robust anti‐inflammatory effects; therefore, it is hypothesized that cis‐aconitate decarboxylase (Acod1)‐produced has a protective, effect during diet‐induced obesity disease. Methods Wild‐type Acod1 −/− mice were subjected obesity. Glucose was...
Mineralocorticoid receptor (MR) blockade has been shown to suppress cardiac hypertrophy and remodeling in animal models of pressure overload (POL). This study aims determine whether MR deficiency myeloid cells modulates aortic constriction-induced cardiovascular injuries. Myeloid knockout (MMRKO) mice littermate control were subjected abdominal constriction (AAC) or sham operation. We found that AAC-induced fibrosis significantly attenuated MMRKO mice. Expression genes important generating...
The interplay between systemic metabolism and immune responses is increasingly recognized as a significant factor in the dysregulation of glucose homeostasis associated with diabetes obesity. Immune metabolites play crucial roles mediating this crosstalk, itaconate emerging an important metabolite involved inflammatory response macrophages. Recent studies have highlighted role regulator metabolism, particularly context obesity, although underlying mechanisms remain poorly understood. In...
Mineralocorticoid receptor (MR) antagonists have protective effects in the brain during experimental ischemic stroke, and we previously demonstrated a key role for myeloid MR stroke pathogenesis. In this study, explore both model- sex-specific actions of stroke.The antagonist eplerenone significantly reduced infarct size male (control, 99.5 mm(3); eplerenone, 74.2 n=8 to 12 per group) but not female 84.0 83.7 n=6 7 mice after transient (90-minute) middle cerebral artery occlusion. contrast...
This study showed, for the first time, role of endogenous IL4Rα signaling in myeloid cells during cardiac remodeling and underlying mechanisms. We identified are critical target cell types post-MI. Deficiency causes deteriorated function post-MI, due to dysregulated inflammation insufficient fibrotic remodeling. sheds light on potential activating myeloid-specific modify brings hope patients with MI diminishes side effects by type-specific instead whole body treatment.
Abstract Objective Excess dietary fat and sodium (NaCl) are both associated with obesity metabolic dysfunction. In mice, high NaCl has been shown to block high‐fat (HF) diet–induced weight gain. Here, the impact of an HF/NaCl diet on function in absence was investigated. Methods Wild‐type mice were administered chow, (4%), HF, diets. Metabolic analysis performed by measuring fasted blood glucose insulin levels tolerance test test. Results After 10 weeks diets, male female HF gained weight,...
Background Hypertension-induced cardiovascular remodeling is characterized by chronic low-grade inflammation. Interleukin-4 receptor α (IL-4Rα) signaling importantly involved in remodeling, however, the target cell type(s) unclear. Here, we investigated role of myeloid-specific IL-4Rα induced angiotensin II and high salt. Methods Results Myeloid deficiency suppressed both vitro vivo expression alternatively activated macrophage markers including Arg1 (arginase 1), Ym1 (chitinase 3-like 3),...
Introduction: Cardiac remodeling post myocardial infarction (MI) can be a critical determinant of outcome for patients with MI. Well-contained inflammation results in successful infarct healing while excessive cause adverse which leads to heart failure. Macrophages are important participants inflammation, helping resolve pro-inflammatory reactions and performing reparative processes. Reprogramming macrophages towards resolving phenotype is potential therapeutic approach. We hypothesized that...
The purpose of this study was to determine whether simultaneous treatment with celecoxib (CEL) interferes the anti‐platelet effects aspirin (ASA). Patients at risk for adverse cardiovascular events often are prescribed a low dose (81 mg) ASA selectively inhibit cyclooxygenase (COX)‐1 dependent synthesis thromboxane A2 in platelets. Many these patients simultaneously administered COX‐2 specific inhibitor, CEL, pain management. Recent vitro reports demonstrated ability CEL bind COX‐1 thereby...
Background: Neutrophils respond rapidly to cerebral ischemia and are thought contribute inflammation-mediated injury during stroke. Neutralizing antibodies inhibition of neutrophil chemotactic molecules can be protective models stroke, but many these techniques have the potential result in cross-reactivity non-specificity with other immune cell types. Using myeloid Mcl1 knockout mice as a model genetic deficiency, we investigated contribution neutrophils stroke pathophysiology. Methods:...
Abstract Background Inflammation is a hallmark of inflammatory bowel disease and alterations in tricarboxylic acid cycle (TCA) metabolism have been identified as major regulators immune cell phenotype during inflammation hypoxia. The TCA metabolite, itaconate, produced by the enzyme aconitate decarboxylase 1 (Acod1) highly upregulated classical macrophage activation experimental colitis. Itaconate permeable derivatives robust anti-inflammatory effects on macrophages, therefore we...