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Browsing by Author "Mitchell, J.A."
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COX-1, and not COX-2 activity, regulates airway function : Relevance to aspirin-sensitive asthma
Harrington, L.S.; Lucas, R.; McMaster, S.K.; Moreno, L.; Scadding, G.; Mitchell, J.A.; Warner, T.D. (2008-11-01)Cyclooxygenase (COX) -1 and COX-2 are expressed in airway cells, where their activities influence functions such as airway hyperreactivity. Clinical data show that mixed COX-1/COX-2 inhibitors such as aspirin, but not COX-2 ... -
Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system
Kirkby, N.S.; Lundberg, M.H.; Harrington, L.S.; Leadbeater, P.D.M.; Potter, C.M.F.; Al-Yamani, M.; Adeyemi, O.; Mitchell, J.A.; Warner, T.D.; Milne, G.L. (2012-10-23)Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production ... -
Effects of Apamin and Charybdtoxin on Endothelium Independent Vasodilatation : Implications in the study of EDHF
MacKenzie, Louise Susan; Carrier, M.J.; Mitchell, J.A. (2005-12)Endothelial derived hyperpolarizing factor (EDHF), together with endothelial derived NO and prostacyclin represent the major endogenous vasodilator hormone pathways (Coleman et al, 2004). Since the chemical nature of EDHF ... -
Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels
Harrington, L.S.; Mitchell, J.A.; Carrier, M.J.; Gallagher, N.; Garland, C.J.; Gilroy, D. (2007-09-01)Although the endothelium co-generates both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the relative contribution from each vasodilator is not clear. In studies where the endothelium is stimulated ... -
Homeostatic role of toll-like receptor 4 in the endothelium and heart
Harrington, L.S.; Belcher, E.; Moreno, L.; Mitchell, J.A.; Carrier, M.J. (2007-12)Toll-like receptor 4 (TLR4) is a pattern recognition receptor for lipopolysaccharide from Gram negative bacteria and thus is integral to the innate immune response in mammals. In addition, TLR4 is associated with atherosclerosis ... -
LC-MS/MS Confirms That COX-1 Drives Vascular Prostacyclin Whilst Gene Expression Pattern Reveals Non-Vascular Sites of COX-2 Expression
Kirkby, N.S.; Zaiss, A.K.; Urquhart, P.; Jiao, J.; Austin, P.J.; Al-Yamani, Malak; Lundberg, M.H.; MacKenzie, Louise; Warner, T.D.; Nicolaou, A.; Herschman, H.R.; Mitchell, J.A. (2013-07-09)There are two schools of thought regarding the cyclooxygenase (COX) isoform active in the vasculature. Using urinary prostacyclin markers some groups have proposed that vascular COX-2 drives prostacyclin release. In contrast, ... -
Making anti-thrombotic bypass vessels from selected populations of vascular smooth muscle cells
Dhanji, A.A.; Ali, F.Y.; MacKenzie, Louise Susan; Shipolini, A.; Mitchell, J.A.; Warner, T.D. (2010-06)Objectives: Vein grafts are commonly used for coronary artery bypass surgery but poor long-term patency and high failure rate make the idea of ‘designer’ bypass vessels attractive. Here we have investigated the possibility ... -
Novel role for P2X receptor activation in endothelium-dependent vasodilation
Harrington, L.S.; Mitchell, J.A. (2004-11-01)ATP is an important vasoactive mediator, which acts via two receptor classes: P2X and P2Y. Activation of P2X receptors has traditionally been associated with the well-characterised vasoconstrictor properties of ATP. In the ... -
Nucleotide oligomerization domain 1 is a dominant pathway for NOS2 induction in vascular smooth muscle cells : Comparison with Toll-like receptor 4 responses in macrophages
Moreno, L.; McMaster, S.K.; Gatheral, T.; Bailey, L.; Harrington, L.; Cartwright, N.; Armstrong, P.C.J.; Warner, T.D.; Paul-Clark, M.; Mitchell, J.A. (2010-08)Background and purpose: Gram-negative bacteria contain ligands for Toll-like receptor (TLR) 4 and nucleotide oligomerization domain (NOD) 1 receptors. Lipopolysaccharide (LPS) activates TLR4, while peptidoglycan products ... -
P2X receptors and the endothelium
Harrington, L.S.; Mitchell, J.A. (2005)Adenosine triphosphate (ATP) is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted ... -
Pharmacology of airways and vessels in lung slices in situ : Role of endogenous dilator hormones
Moreno, L.; Perez-Vizcaino, F.; Harrington, L.; Faro, R.; Sturton, G.; Barnes, P.J.; Mitchell, J.A. (2006-08-21)Small airway and vessels play a critical role in chronic airway and pulmonary vascular diseases, but their pharmacology has not been well characterised. We have studied airway and vascular responses in rat lung slices and ... -
The PPAR target gene CD36 is a rate limiting factor for the sensing of gram positive S-aureus in vascular smooth muscle cells but not in macrophages
Moreno, L.; McMaster, S.K.; Paul-Clark, M.; MacKenzie, Louise Susan; Cartwright, N.; Secher, T.; Quesniaux, V.; Ryffel, B.; Mitchell, J.A. (2008-08-01)Bacteria activate macrophages and vascular smooth muscle cells (VSMCs) resulting in induction of nitric oxide synthase (NOS)II activity. Here we show that the PPARc agonist rosiglitazone (rosi) increases the sensing of ... -
The PPARβ/δagonist GW0742 relaxes pulmonary vessels and limits right heart hypertrophy in rats with hypoxia-induced pulmonary hypertension
Harrington, L.S.; Moreno, L.; Reed, A.; Mitchell, J.A.; Wort, S.J.; Desvergne, B.; Garland, C.; Zhao, L. (2010-03-04)Background: Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive ... -
Purinergic 2X receptors mediate endothelial dependent vasodilation to ATP
Harrington, L.S.; Ali, F.; Mitchell, J.A.; Wray, J.; Swales, K.E.; Norling, L.; Evans, R.J.; Vial, C.; Carrier, M.J. (2007-11)ATP is an important endogenous mediator in the cardiovascular system. It induces endothelium dependent vasodilation, but the precise receptor pathway activated in this response is currently under debate. We have used ... -
Reduced endothelial dependent vasodilation in vessels from TLR4 mice is associated with increased superoxide generation
Harrington, L.S.; Lundberg, M.H.; Waight, M.; Rozario, A.; Mitchell, J.A. (2011-05-20)Toll like receptor (TLR)4 is a pattern recognition receptor expressed in endothelial and other cells, responsible for the sensing of endotoxin and host derived ligands. Our group has shown previously that the absence of ... -
Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium
Mitchell, J.A.; Ali, F.; Bailey, L.; Moreno, L.; Harrington, L.S. (2008-01)The endothelium lines the luminal surface of every blood vessel, allowing it contact with circulating blood elements, as well as the underlying vascular smooth muscle layer. In healthy vessels, the endothelium expresses ... -
Role of RhoB in the regulation of pulmonary endothelial and smooth muscle cell responses to hypoxia
Wojciak-Stothard, B.; Zhao, L.; Oliver, E.; Dubois, O.; Wu, Y.; Kardassis, D.; Vasilaki, E.; Mitchell, J.A.; Huang, M.; MacKenzie, Louise Susan; Prendergast, G.C.; Wilkins, M.R. (2012-05-25)Rationale: RhoA and Rho kinase contribute to pulmonary vasoconstriction and vascular remodeling in pulmonary hypertension. RhoB, a protein homologous to RhoA and activated by hypoxia, regulates neoplastic growth and ... -
Role of shear stress in endothelial cell morphology and expression of cyclooxygenase isoforms
Potter, C.M.F.; Lundberg, M.H.; Harrington, L.S.; Moshkov, A.V.; Gorelik, J.; Mitchell, J.A.; Warboys, C.M.; Weinberg, P.D.; Warner, T.D.; Berson, R.E. (2011-02)Objective-: The goal of this study was to examine the effect of chronic heterogeneous shear stress, applied using an orbital shaker, on endothelial cell morphology and the expression of cyclooxygenases 1 and 2. Methods and ... -
Role of the endothelium and COX-1 in prostacyclin generation by whole vessels stimulated with different agonists
Alyamanil, Malak; Kirkby, N.S.; MacKenzie, Louise Susan; Lundberg, M.H.; Warner, T.D.; Mitchell, J.A. (2012)Prostacyclin is an important cardioprotective hormone produced by the vascular wall, whose synthesis is dependent on cyclo-oxygenase (COX) enzymes. In healthy vessels the endothelium is thought to be the main site of ...