Angiotensin II Receptor Antagonist TCV-116 Reduces Graft Coronary Artery Disease and Preserves Graft Status in a Murine Model

Furukawa, Yutaka; Matsumori, Akira; Hirozane, Toshiro; Sasayama, Shígetake

doi:10.1161/01.cir.93.2.333

Cited by 66 publications

(48 citation statements)

References 37 publications

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“…A recruitment of T cells in TI of the kidney, as documented by CD 4 and CD 8 staining, could be observed in Ang II-infused rats. When infused rats were treated with high-dose olmesartan, T-cell infiltration was absent.…”

Section: Ti Injury In Ang Ii-infused Ratsmentioning

confidence: 75%

Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury

et al. 2003

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Abstract-Blockade of angiotensin (Ang) II is efficient in various renal diseases. Although interest has focused on the hemodynamic changes and reduction of proteinuria, recent studies emphasize the nonhemodynamic effects of Ang II on kidney injury. The aim of this study was to clarify the mechanisms of Ang II on the immune system that alter the balance of helper T-cell (Th) subsets. We used a continuous, Ang II infusion model of rats that develop hypertension, proteinuria, and tubulointerstitial damage, including de novo expression of ␣-smooth muscle actin and loss of endothelial cells. We isolated T cells from the spleen and measured cytokine levels by ELISA systems. Ang II-infused rats showed an increase in the Th1 cytokine ␥-interferon and a decrease in the Th2 cytokine interleukin-4. The same change in cytokine mRNA expression in the spleen and kidney was confirmed by quantitative polymerase chain reaction analysis. Our ELISPOT assay showed an increase in the number of ␥-interferon-secreting T cells by Ang II. To investigate whether these changes were specific effects of Ang II, we treated the model rats with the Ang II receptor blocker (ARB) olmesartan or the nonspecific vessel dilator hydralazine. Administration of the ARB ameliorated disease manifestations and the imbalance in Th subsets, whereas hydralazine did not, despite comparable effects on blood pressure. These results demonstrate a direct role of Ang II in the modification of Th balance. T he renin-angiotensin system has been a target for research on hypertension for a long time. This system plays a crucial role in regulating a variety of renal functions, such as blood pressure (BP) and electrolyte and water homeostasis.

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Section: Ti Injury In Ang Ii-infused Ratsmentioning

confidence: 75%

Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury

et al. 2003

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“…In contrast, other strategies have sought to directly inhibit VSMC proliferation, a late component of transplant arteriosclerosis (5,48). It has been shown that receptor antagonists for VSMC mitogens (49,50) and rapamycin (51-53), a potent VSMC growth inhibitor, are effective at inhibiting chronic graft vasculopathy in animal models. Molecular strategies that target VSMC growth have also been examined in models of chronic graft vasculopathy.…”

Section: Discussionmentioning

confidence: 99%

Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia

Sata

Luo

Walsh

2001

The Journal of Immunology

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Despite recent advances in immunosuppressive therapy, accelerated coronary atherosclerosis remains a major problem in the long-term survival of transplant recipients. Chronic graft vasculopathy is believed to result from recipient inflammatory responses, and it is characterized by early mononuclear cell infiltration of the transplanted vessel. Here we show that endothelial cells can be genetically modified to overexpress functional, cell-surface Fas ligand (FasL) by adenovirus-mediated gene transfer without undergoing self-destruction. In a rodent model of transplant graft vasculopathy, endothelial overexpression of FasL attenuated T cell and macrophage infiltration at 1 wk posttransplantation. These vessels also displayed reduced neointima formation at one and 2 mo posttransplantation. These results indicate that inhibition of the early inflammatory response to allografted vessels by endothelial cell-specific overexpression of FasL may have utility in the treatment of transplant arteriosclerosis.

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“…However, NF B decoy markedly attenuated myocardial cell infiltration, the score was statistically less than those of the other groups. Immunohistochemically, [14][15][16] native hearts and isografts showed no enhancement of ICAM-1, VCAM-1, MHC class I, MHC class II or NF B expression. These were enhanced in nontreated or scrambled ODN transfected allografts of minor mismatch group at day 28, mainly observed in myocardial interstitium with mononuclear cell infiltration.…”

Section: Graft Survivalmentioning

confidence: 99%

“…Sections were incubated with primary antibodies against murine intercellular adhesion molecule (ICAM)-1 (YN1/1.7), vascular cell adhesion molecule (VCAM)-1 (MK/2) (provided by Prof Ko Okumura, Juntendo University, Japan), MHC class I and class II (Funakoshi, Tokyo, Japan) and NF B (Santa Cruz Biotechnology, Santa Cruz, CA, USA) for 12 h at 4°C. [14][15][16] Antibody-biotin conjugate was detected with Vectastain ABC Kit (Vector, Burlingame, CA, USA) used according to the manufacturer's instructions. Enzyme activity was detected with diaminobenzidine (0.5 mg/ml) with 0.05% NiCl in 50 mm Tris buffer, pH 7.5.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

et al. 2000

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Acute rejection and graft arteriopathy in cardiac transplantation limit the long-term survival of recipients; these processes are enhanced by several cytokines and adhesion molecules. Nuclear factor-kappa B (NF B) is critical in the transcription of multiple genes involved in inflammation and cell proliferation. To test the hypothesis that NF B decoy can attenuate acute rejection and arteriopathy, we performed single intraluminal delivery of NF B decoy into murine cardiac allografts using a hemagglutinating virus of Japan (HVJ)-artificial viral envelope (AVE)-liposome method. No decoy or scrambled decoy transfer was performed for control. Hearts were heterotopically transplanted from BALB/c to C3H/He mice (major mismatch group) and from DBA/2 to

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Angiotensin II Receptor Antagonist TCV-116 Reduces Graft Coronary Artery Disease and Preserves Graft Status in a Murine Model

Abstract: These findings show that AT1-R blockade is at least as effective as ACE inhibition in management of chronic allograft rejection and suggest that Ang II may play an important role in chronic allograft rejection.

Cited by 66 publications

References 37 publications

Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury

Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury

Fas Ligand Overexpression on Allograft Endothelium Inhibits Inflammatory Cell Infiltration and Transplant-Associated Intimal Hyperplasia

Decoy against nuclear factor-kappa B attenuates myocardial cell infiltration and arterial neointimal formation in murine cardiac allografts

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