A5084268088- Angiogenesis and VEGF in Cancer
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Lipoproteins and Cardiovascular Health
- Antiplatelet Therapy and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- Hormonal Regulation and Hypertension
- Cerebrovascular and Carotid Artery Diseases
- Pharmacogenetics and Drug Metabolism
- Coronary Interventions and Diagnostics
- Cancer, Lipids, and Metabolism
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Peripheral Artery Disease Management
- Immune Response and Inflammation
- High Altitude and Hypoxia
- Immune Cell Function and Interaction
- Ginger and Zingiberaceae research
- Sepsis Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Apelin-related biomedical research
- Inflammatory mediators and NSAID effects
- Hydrogen's biological and therapeutic effects
- MicroRNA in disease regulation
- Renin-Angiotensin System Studies
Loyola University Chicago
2022-2025
University of Chicago
2023-2025
SUNY Upstate Medical University
2011-2024
Syracuse VA Medical Center
2011-2024
Newcastle upon Tyne Hospitals NHS Foundation Trust
2022-2023
Freeman Hospital
2022-2023
Newcastle University
2022-2023
Rush University Medical Center
2022
Loyola University Medical Center
2022
New York/New Jersey VA Health Care Network
2008-2020
Sepsis and hemorrhage can result in injury to multiple organs is associated with an extremely high rate of mortality. We hypothesized that peritoneal negative pressure therapy (NPT) would reduce systemic inflammation organ damage. Pigs (n = 12) were anesthetized surgically instrumented for hemodynamic monitoring. Through a laparotomy, the superior mesenteric artery was clamped 30 min. Feces mixed blood form fecal clot placed into peritoneum, abdomen closed. All subjects treated standard...
The present study examined the effects of ANG II on renal synthesis 20-hydroxyeicosatetraenoic acid (20-HETE) and its contribution to vasoconstrictor acute chronic pressor in rats. (10(-11) 10(-7) mol/l) reduced diameter interlobular arteries treated with inhibitors nitric oxide synthase cyclooxygenase, lipoxygenase, epoxygenase by 81 +/- 8%. Subsequent blockade 20-HETE 17-octadecynoic (1 micromol/l) increased ED(50) for II-induced constriction a factor 15 diminished maximal response 61%....
This study characterized myogenic activation of skeletal muscle (gracilis) resistance arteries from lean (LZR) and obese Zucker rats (OZR). Arteries OZR exhibited increased versus LZR; this increase was impaired by endothelium denudation or nitric oxde synthase inhibition. Treatment vessels with 17-octadecynoic acid responses in both strains comparable amounts. Dihydroethidine microfluorography indicated elevated vascular superoxide levels immunohistochemistry demonstrated nitrotyrosine OZR,...
This study examined the effects of blocking formation 20-hydroxyeicosatetraenoic acid (20-HETE) on acute fall in cerebral blood flow after subarachnoid hemorrhage (SAH) rat. In vehicle-treated rats, regional (rCBF) measured with laser-Doppler flowmetry fell by 30% 10 min injection 0.3 ml arterial into cisterna magna, and it remained at this level for 2 h. Pretreatment inhibitors 20-HETE, 17-octadecynoic (17-ODYA; 1.5 nmol intrathecally) N-hydroxy- N′-(4-butyl-2-methylphenyl)formamidine...
Objective: To gain insights into individual variations in acute inflammation and physiology. Design: Large-animal study combined with mathematical modeling. Setting: Academic large-animal computational laboratories. Subjects: Outbred juvenile swine. Interventions: Four swine were instrumented subjected to endotoxemia (100 µg/kg), followed by serial plasma sampling. Measurements Main Results: Swine exhibited various degrees of lung injury, including one death severe injury (PaO2/FIO2 ratio...
The present study examined whether 20-hydroxyeicosatetraenoic acid (HETE) contributes to the vasoconstrictor effect of angiotensin II (ANG II) in renal microvessels by preventing activation large conductance Ca2+-activated K+ channel (KCa) vascular smooth muscle (VSM) cells. ANG increased production 20-HETE rat microvessels. This response was attenuated synthesis inhibitors, 17-ODYA and HET0016, a phospholipase A2 inhibitor AACOF3, AT1 receptor blocker, Losartan, but not AT2 PD123319. (10-11...
Vascular endothelial growth factor (VEGF) has been implicated in angiogenesis induced by electrical stimulation skeletal muscle. Less is known about the role of arachidonic acid metabolites control blood vessels vivo. The present study examined 20-hydroxyeicosatetraenoic (20-HETE) on tibialis anterior and extensor digitorum longus muscles rats were stimulated for 7 days. Electrical significantly increased 20-HETE formation muscles, which was blocked chronic treatment with N-hydroxy-...
The present study evaluated whether reactive oxygen species–induced alterations in bioavailability of 20-HETE the kidney contribute to antihypertensive and renoprotective actions antioxidant therapy with Tempol Dahl salt-sensitive (DS) rat. Superoxide inhibited synthesis by renal cortical microsomes enhanced breakdown a more polar product. Addition (1 mmol/L) drinking water reduced mean arterial pressure from 187±9 160±3 mm Hg DS rats fed an 8%-NaCl diet for 2 weeks. excretion rose 117±11...
Background: Statins have beneficial pleiotropic effects, including reducing intimal hyperplasia (IH), but off-target effects remain a concern. Here, we tested the hypothesis that chitosan-functionalized polymeric nanoparticles (NPs) loaded with simvastatin (SL-cNPs) would (1) readily associate endothelial cells (ECs) and vascular smooth muscle (VSMCs); (2) affect EC VSMC function; (3) reduce IH compared to systemic simvastatin. Methods: Human aortic ECs VSMCs were cultured fluorescently...
Thrombospondins (TSPs) are matricellular proteins involved in intimal hyperplasia (IH). We hypothesized: (1) TSP-1, -2 and -5 interdependent regarding their effects on vascular smooth muscle (VSMC) physiology; (2) local or systemic knock-out of TSP-1 ( THBS1) THBS2 reduces IH, with its combination THBS1/2) being most effective; (3) THBS5 increases IH; (4) the TSPs differ between males females. In vitro, VSMCs were transfected siRNA against THBS1, THBS2, THBS1/2 . VSMC proliferation by...
Mediator contributions to hypoxic dilation of rat gracilis muscle resistance arteries were determined by measuring dilation, vascular smooth hyperpolarization, and metabolite production after incremental hypoxia. Nitric oxide (NO) synthase inhibition abolished responses mild hypoxia, whereas COX impaired more severe hypoxia 77%. Blocking 20-hydroxyeicosatetraenoic acid (20-HETE) moderate With only NO systems intact, maintained with (88% normal) mediated via K(Ca) channels. When pathways...
NO synthase (NOS) can paradoxically contribute to the production of reactive oxygen species when l -arginine or cofactor R-tetrahydrobiopterin (BH 4 ) becomes limited. The present study examined whether NOS contributes superoxide in kidneys hypertensive Dahl salt-sensitive (SS) rats compared with an inbred consomic control strain (SS-13 BN and tested hypothesis that elevated dihydrobiopterin 2 levels are importantly involved this process. This was assessed by determining effects...
This study examined the mechanism by which cGMP contributes to vasodilator response nitric oxide (NO) in rat middle cerebral arteries (MCA). Administration of a NO donor, diethylaminodiazen-1-ium-1,2-dioate (DEA-NONOate), or 8-bromo-cGMP (8-BrcGMP) increased diameter serotonin-preconstricted MCA 79 ± 3%. The DEA-NONOate, but not 8-BrcGMP, was attenuated iberiotoxin (10 −7 M) 80 mM high-K + media, suggesting that activation K channels 8-BrcGMP. effects and on vasoconstrictor Ca 2+ were also...
This study describes a fluorescent HPLC assay for measuring 20-hydroxyeicosatetraenoic acid (20-HETE) and other cytochrome P-450 metabolites of arachidonic in urine, tissue, interstitial fluid. An internal standard, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, was added to samples, the lipids were extracted labeled with 2-(2,3-naphthalimino)ethyl trifluoromethanesulfonate. separated on C18 reverse-phase column. Coelution gas chromatography-mass spectrometry studies confirmed identity 20-HETE...
In contrast to its constrictor effects on peripheral arteries, 20-hydroxyeicosatetraenoic acid (20-HETE) is an endothelial-dependent dilator of pulmonary arteries (PAs). The present study examined the hypothesis that vasodilator 20-HETE in PAs are due elevation intracellular calcium concentration ([Ca 2+ ] i ) and release nitric oxide (NO) from bovine PA endothelial cells (BPAECs). BPAECs express cytochrome P-450 4A (CYP4A) protein produce 20-HETE. dilated preconstricted with U-46619 or...