Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury

Matsuyama, Masahide; Yoshimura, Rikio; Akioka, Kiyokazu; Okamoto, Masahiko; Ushigome, Hidetaka; Kadotani, Yayoi; Nakatani, Tatsuya; Yoshimura, Norio

doi:10.1097/01.tp.0000079630.68668.c2

Cited by 43 publications

(33 citation statements)

References 20 publications

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“…Contrasting with this progress, the half-life of the transplants has remained the same due to chronic allograft nephropathy (CAN), 3 which represents a major cause for graft loss after the first year of transplantation (1). The pathophysiology of CAN remains elusive.…”

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confidence: 99%

Hydrolysis of Coagulation Factors by Circulating IgG Is Associated with a Reduced Risk for Chronic Allograft Nephropathy in Renal Transplanted Patients

Wootla

Nicoletti

Patey

et al. 2008

The Journal of Immunology

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Chronic allograft nephropathy (CAN), a major cause of late allograft failure, is characterized by a progressive decline in graft function correlated with tissue destruction. Uncontrolled activation of the coagulation cascade by the stressed endothelium of the graft is thought to play an important role in the pathophysiology of CAN. In this study, we demonstrate that circulating IgG from renal-transplanted patients are endowed with hydrolytic properties toward coagulation factors VIII and IX, but fail to hydrolyze factor VII and prothrombin. The hydrolytic activity of IgG was reliably quantified by the measure of the hydrolysis of a fluorescent synthetic substrate for serine proteases: proline-phenylalanine-arginine-methylcoumarinamide (PFR-MCA). A retrospective case-control study indicated that an elevated hydrolysis rate of PFR-MCA by circulating IgG correlated with the absence of CAN lesions on protocol graft biopsy performed 2 years posttransplantation. We propose that circulating hydrolytic IgG may counterbalance the procoagulation state conferred by the activated endothelium by disrupting the amplification loop of thrombin generation which is dependent on factors VIII and IX. Interestingly, low rates of PFR-MCA hydrolysis, measured 3 mo posttransplantation, were predictive of CAN at 2 years down the lane. These data suggest that PFR-MCA hydrolysis may be used as a prognosis marker for CAN in renal-transplanted patients.

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mentioning

confidence: 99%

Hydrolysis of Coagulation Factors by Circulating IgG Is Associated with a Reduced Risk for Chronic Allograft Nephropathy in Renal Transplanted Patients

Wootla

Nicoletti

Patey

et al. 2008

The Journal of Immunology

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“…[10][11][12][13][14] TF on monocytes and synovial cells promotes leukocyte adhesion and transendothelial migration, potentiating inflammation in joints, 15 while decreased TF activity abrogates the systemic expression of inflammatory mediators in several animal models. 16,17 The antiphospholipid syndrome (APS) is considered a thrombophilic disorder. However, animal studies from our laboratory have shown the importance of inflammation in the pathogenesis of aPL-induced pregnancy loss, a common complication in APS.…”

Section: Introductionmentioning

confidence: 99%

Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody–induced fetal injury

Redecha

Tilley

Tencati

et al. 2007

Blood

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270

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Fetal loss in patients with antiphospholipid (aPL) antibodies has been ascribed to thrombosis of placental vessels. However, we have shown that inflammation, specifically activation of complement with generation of the anaphylotoxin C5a, is an essential trigger of fetal injury. In this study, we analyzed the role of the procoagulant molecule tissue factor (TF) in a mouse model of aPL antibody-induced pregnancy loss. We found that either blockade of TF with a monoclonal antibody in wild-type mice or a genetic reduction of TF prevented aPL antibodyinduced inflammation and pregnancy loss. In response to aPL antibody-generated C5a, neutrophils express TF potentiating inflammation in the deciduas and leading to miscarriages. Importantly, we showed that TF in myeloid cells but not fetal-derived cells (trophoblasts) was associated with fetal injury, suggesting that the site for pathologic TF expression is neutrophils. We found that TF expression in neutrophils contributes to respiratory burst and subsequent trophoblast injury IntroductionThrombosis and inflammation are linked in many clinical conditions. 1 Tissue factor (TF), the major cellular initiator of the coagulation protease cascade, plays important roles in both thrombosis and inflammation. 2 The coagulation cascade is initiated by the complex of TF and factor VIIa (FVIIa). The TF:FVIIa complex activates its substrates factor X and factor IX by limited proteolysis. Activated FX (FXa) then converts prothrombin to thrombin, which cleaves fibrinogen and activates platelets leading to the formation of a hemostatic plug. TF also contributes to inflammation. TF complexes (TF:FVIIa and TF:FVIIa:FXa) induce the expression of TNF-␣, interleukins, and adhesion molecules by cleaving protease activated receptors (PARs). [3][4][5] Monocytes from patients with antiphospholipid (aPL) antibodies express TF and in vitro experiments showed that monocytes incubated with aPL antibodies express TF. 6,7 A variety of inflammatory stimuli, including mitogens, bacterial cell products, components of the complement system, and cytokines, is known to induce the expression of TF on the surface of endothelial cells, monocytes, and neutrophils. 8,9 TF expression on these cells is a characteristic feature of acute and chronic inflammation in conditions such as sepsis, atherosclerosis, Crohn disease, systemic lupus erythematosus, and transplant rejection reactions. 10-14 TF on monocytes and synovial cells promotes leukocyte adhesion and transendothelial migration, potentiating inflammation in joints, 15 while decreased TF activity abrogates the systemic expression of inflammatory mediators in several animal models. 16,17 The antiphospholipid syndrome (APS) is considered a thrombophilic disorder. However, animal studies from our laboratory have shown the importance of inflammation in the pathogenesis of aPL-induced pregnancy loss, a common complication in APS. 18,19 Using a mouse model of APS, we demonstrated that complement activation, through the action of anaphylotoxin C5a, promotes neutrop...

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“…Renal ischemiareperfusion (I/R) injury is a clinically significant problem and an invariable consequence of renal transplantation that results from aortic cross-clamping and resuscitation after systemic hypotension. Previous studies have focused on the function of neutrophils, the action mechanisms of inflammatory cytokines, tissue factors, intercellular adhesion molecule-1, oxygen-free radicals, vascular plugging, edema and other complications (1).…”

Section: Introductionmentioning

confidence: 99%

Relationship between peroxisome proliferator-activated receptor-γ and renal ischemia-reperfusion injury

Matsuyama

Yoshimura²,

Kawahito³

et al. 2008

Mol Med Report

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Abstract. The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and, in particular, surface adhesion molecules, the expression of which initiates inflammatory cell attachment. It has been suggested that peroxisome proliferator-activated receptor (PPAR)-γ is an important immunomodulatory factor as well as a regulator of fatty acid. In this study, we investigated the expression of PPAR-γ in a renal I/R injury rat model. The right kidney was harvested and the left renal artery and vein were clamped by means of a laparotomy. The kidney was reperfused following 90 min of ischemia. Rats were sacrificed at 0, 1.5, 3, 5, 12 and 24 h after reperfusion. PPAR-γ expression was analyzed by immunohistochemical staining using monoclonal antibody. PPAR-γ staining was weak in the endothelial cells, interstitial cells and collecting ducts in the normal kidney. From 1.5 to 5 h after reperfusion, PPAR-γ staining was strong. Twelve hours after reperfusion, necrosis had extended throughout the kidney, and nearly all the tubular epithelial cells were destroyed. However, 12 h after reperfusion, PPAR-γ staining was weak in the endothelial cells and its expression was moderate in the interstitial cells and collecting ducts. PPAR-γ was induced in the endothelial cells, including the mesangial cells, interstitial cells and collecting ducts in a rat model of renal I/R injury. IntroductionRenal transplantation is an acceptable therapeutic approach for patients with end-stage renal disease. Renal ischemiareperfusion (I/R) injury is a clinically significant problem and an invariable consequence of renal transplantation that results from aortic cross-clamping and resuscitation after systemic hypotension. Previous studies have focused on the function of neutrophils, the action mechanisms of inflammatory cytokines, tissue factors, intercellular adhesion molecule-1, oxygen-free radicals, vascular plugging, edema and other complications (1).Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcriptional factors, which includes receptors for steroids, thyroid hormones, vitamin D 3 and retinoic acid. PPAR binds to a peroxisome proliferator responsive element to form a heterodimer with the retinoic receptor in the regulation of PPAR target genes (2).There are three known PPAR isoforms: PPAR-α, -ß and -γ. PPAR-α primarily regulates the fatty acid metabolism and has an anti-inflammatory effect; its ligands are used in fibrate drugs. PPAR-ß is ubiquitously expressed throughout the body, but its physiological functions are unknown. PPAR-γ has anti-inflammatory effects and controls the functioning of the immune system, having inhibitory action on the production of nitric oxide, cytokine and monocyte chemoattractant protein-1 and on B-cell growth, vascularization and cell growth, and differentiation-inducing action on dendritic cells and helper T-cells (3).PPAR-γ has also been implicated in inflammation and tumorigenesis (4), and significant evidenc...

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Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury

Abstract: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.

Cited by 43 publications

References 20 publications

Hydrolysis of Coagulation Factors by Circulating IgG Is Associated with a Reduced Risk for Chronic Allograft Nephropathy in Renal Transplanted Patients

Hydrolysis of Coagulation Factors by Circulating IgG Is Associated with a Reduced Risk for Chronic Allograft Nephropathy in Renal Transplanted Patients

Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody–induced fetal injury

Relationship between peroxisome proliferator-activated receptor-γ and renal ischemia-reperfusion injury

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