Urinary thromboxane A2/prostacyclin balance reflects the pathological state of a diabetic

Hishinuma, Takanori; Koseki, Yuko; Murai, Yuriko; Yamazaki, Tohru; Suzuki, Ken; Mizugaki, Michinao

doi:10.1016/s0090-6980(99)00029-5

Cited by 30 publications

(17 citation statements)

References 20 publications

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“…The increased expression of LOX enzymes has been implicated in the vascular pathogenesis and renal injury associated with diabetes [46,[128][129][130]. The 5-LOX enzymes and LTE 4 generation have been associated with diabetes [131].…”

Section: Renal Vascular Eicosanoids In Diabetes and Metabolic Syndromementioning

confidence: 99%

Eicosanoids and renal vascular function in diseases

Imig

2006

Clinical Science

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Arachidonic acid metabolites are vital for the proper control of renal haemodynamics and, when not properly controlled, can contribute to renal vascular injury and end-stage renal disease. Three major enzymatic pathways, COX (cyclo-oxygenase), CYP450 (cytochrome P450) and LOX (lipoxygenase), are responsible for the metabolism of arachidonic acid metabolites to bioactive eicosanoids. These eicosanoids can dilate or constrict the renal vasculature and maintain vascular resistance in the face of changing vasoactive hormones. Renal vascular generation of eicosanoids is altered in pathophysiological conditions such as hypertension, diabetes, metabolic syndrome and acute renal failure. Experimental evidence supports the concept that altered eicosanoid metabolism contributes to renal haemodynamic alterations and the development and progression of nephropathy. The possible beneficial renal vascular actions of enzymatic inhibitors, eicosanoid analogues and receptor antagonists have been examined in hypertension, diabetes and metabolic syndrome. This review highlights the roles of renal vascular eicosanoids in the pathogenesis of nephropathy and therapeutic targets for renal disease related to hypertension, diabetes, metabolic syndrome and acute renal failure.

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Section: Renal Vascular Eicosanoids In Diabetes and Metabolic Syndromementioning

confidence: 99%

Eicosanoids and renal vascular function in diseases

Imig

2006

Clinical Science

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“…An increase in TX production is widely reported in patients with diabetes mellitus (DM) (47,48) as well as in animal DM models (49,50), which may induce the hypercoagulable state leading to cardiovascular complications including atherosclerosis. Moreover, TX-induced aortic contraction is augmented in diabetic rats (51).…”

Section: Inhibition Of Sp1 Activity By Ppar-␥-mentioning

confidence: 99%

Transcription Suppression of Thromboxane Receptor Gene by Peroxisome Proliferator-activated Receptor-γ via an Interaction with Sp1 in Vascular Smooth Muscle Cells

Sugawara

Uruno

Kudo

et al. 2002

Journal of Biological Chemistry

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Thromboxane (TX)A Thromboxane (TX)1 A 2 is a labile metabolite of arachidonic acid synthesized by TX synthase (1). TX is known to exert many biological effects such as platelet aggregation, contraction and growth of vascular smooth muscle cells (VSMCs) (2, 3), and renal electrolyte metabolism (4). TX is also known to play a pathophysiological role in the inflammatory diseases such as atherosclerosis (5) and glomerulonephritis (6). The biological action of TX is mediated via its specific membrane TX receptor (TXR). We previously isolated a cDNA for rat TXR (7), localized it in either the kidney (8) or testis (9), and identified its chromosomal localization (10). Moreover, we have isolated 5Ј-flanking region (FL) of the rat TXR gene and studied its transcription regulation in VSMCs (11).Peroxisome proliferator-activated receptor (PPAR)-␥ is a nuclear hormone receptor that was shown to transactivate adipocyte-specific genes and induce adipocyte differentiation (12). Either insulin-sensitizing thiazolidinediones including troglitazone (TRO) or 15-deoxy-⌬ 12,14 -prostaglandin J 2 (PGJ 2 ) (13, 14) has been identified as a ligand of PPAR-␥. Recently, PPAR-␥ has been shown to be present not only in adipocytes but also in vascular tissues including VSMCs (15), and an inhibitory effect of PPAR-␥ on gene expression in atherosclerosis has been studied. Activation of PPAR-␥ with its ligands suppressed expression of plasminogen activator inhibitor type 1 (16) in vascular endothelial cells and that of matrix metalloproteinase-9 in VSMCs (15). Moreover, we have observed that PPAR-␥ can suppress TX synthase gene transcription in macrophages (17).In the present study, we examined the role of PPAR-␥ in TXR gene expression in VSMCs. We observed that PPAR-␥ inhibited the TX-mediated cell growth of VSMCs and TXR mRNA expression. Suppression of TXR gene transcription was confirmed, and the suppression was shown to be dependent on a GC box-related sequence present at the Ϫ22/Ϫ7 region of TXR gene promoter (upstream of transcription start site), which was bound by Sp1 but not by PPAR-␥. PPAR-␥ was shown to interact physically with Sp1 by glutathione S-transferase (GST) pull-down assays. Taken together, PPAR-␥ was suggested to suppress TXR gene transcription via a protein-protein interaction with Sp1. An antiatherosclerotic action of PPAR-␥ by inhibiting TXR gene expression in VSMCs may be suggested. EXPERIMENTAL PROCEDURESPlasmids-Previously reported (11) and newly subcloned chimeric constructs containing rat TXR gene promoter and luciferase cDNA were used for transient transfection studies: Ϫ989/ϩ184-luc (989-bp 5Ј-flanking region (FL) and 184-bp 5Ј-untranslated region (UTR) of rat TXR gene); Ϫ809/ϩ184-luc (809-bp 5Ј-FL and 184-bp 5Ј-UTR); Ϫ489/ϩ184-luc (489-bp 5Ј-FL and 184-bp 5Ј-UTR); Ϫ213/ϩ184-luc (213-bp 5Ј-FL and 184-bp 5Ј-UTR); Ϫ78/ϩ184-luc (78-bp 5Ј-FL and 184-bp 5Ј-UTR); Ϫ78/ϩ120-luc (78-bp 5Ј-FL and 120-bp 5Ј-UTR); Ϫ47/ϩ120-luc (47-bp 5Ј-FL and 120-bp 5Ј-UTR); Ϫ39/ϩ120-luc (39-bp 5Ј-FL and 120-bp 5Ј-UTR); Ϫ22/ϩ120-luc (22-bp ...

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“…12,47 In an attempt to determine whether diabetes mellitus was associated with activation of the 5-lipoxygenase pathway, we studied the urinary excretion of LTE 4 in control, SS, and SI rats. LTE 4 excretion was significantly increased in SS rats and positively correlated with glycemia.…”

Section: Lte 4 Excretion In Control Ss and Si Ratsmentioning

confidence: 99%

Cysteinyl Leukotrienes Modulate Angiotensin II Constrictor Effects on Aortas From Streptozotocin-Induced Diabetic Rats

Hardy

Stanke-Labesque

Péoc’h

et al. 2001

ATVB

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Abstract-Angiotensin II (Ang II) is a vasopressor peptide involved in the pathogenesis of cardiovascular diseases associated with diabetes mellitus. We have previously reported that the 5-lipoxygenase-derived products, particularly the cysteinyl leukotrienes (CysLTs), are involved in Ang II-induced contraction. In this study, we demonstrated that CysLTs contribute to the contraction elicited by Ang II in isolated aortas from streptozotocin-induced diabetic (SS) rats but not from insulin-treated diabetic rats, fructose-fed rats, or control rats. In an organ bath, pretreatment with the 5-lipoxygenase inhibitor (AA861, 10 mol/L) reduced by 37.6Ϯ8.2% and 30.1Ϯ10.9% the Ang II-induced contractions in intact and endothelium-denuded aortic rings, respectively, from SS rats. In contrast, the

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Urinary thromboxane A2/prostacyclin balance reflects the pathological state of a diabetic

Cited by 30 publications

References 20 publications

Eicosanoids and renal vascular function in diseases

Eicosanoids and renal vascular function in diseases

Transcription Suppression of Thromboxane Receptor Gene by Peroxisome Proliferator-activated Receptor-γ via an Interaction with Sp1 in Vascular Smooth Muscle Cells

Cysteinyl Leukotrienes Modulate Angiotensin II Constrictor Effects on Aortas From Streptozotocin-Induced Diabetic Rats

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