Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug

Isaji, Masayuki; Miyata, Hiroshi; Ajisawa, Yukiyoshi

doi:10.1111/j.1527-3466.1998.tb00359.x

Cited by 28 publications

(20 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its safety has been established in Ͼ15 years of clinical use. It has received recent attention in the field of cardiovascular medicine as an antiproliferative agent 7,27,28 ; potent inhibitory effects on proliferation and migration of rat 11,29 and human aortic vascular smooth muscle cells 30,31 …”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] N- (3,anthranilic acid (tranilast) has been effective in the treatment of allergic diseases, such as bronchial asthma, allergic rhinitis, and atopic dermatitis. This compound has been shown in hypertensive granulomatous inflammation to inhibit the growth of fibroblasts and suppress collagen accumulation, 6 activities that are recognized as beneficial antiproliferative actions 7 and are clinically effective against keloids and hypertrophic scars. Several recent clinical trials have shown the potent effect of tranilast in preventing restenosis after percutaneous transluminal coronary angioplasty (PTCA) 8 and after directional coronary atherectomy.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Izawa

Suzuki²,

Takahashi³

et al. 2001

ATVB

View full text Add to dashboard Cite

Abstract-Cardiac allograft vasculopathy is a major complication after cardiac transplantation, often limiting long-term recipient survival. N- (3,anthranilic acid (tranilast) inhibits cyclin-dependent kinase activity through p21 Waf1/Cip1 induction and arrests vascular smooth muscle cell proliferation in vitro. We tested a hypothesis that tranilast inhibits the vasculopathy characterized by diffuse intimal thickening in a murine heart transplantation model. Hearts from DBA/2 mice were heterotopically transplanted into B10.D2 mice as allografts. Oral administration of tranilast started 3 days before transplantation at doses of 550 or 1040 mg/kg per day until the animals were killed. Cardiac allograft vasculopathy was defined as luminal stenosis caused by neointimal formation. The percentage of luminal stenosis and cardiac rejection were analyzed 14 and 28 days after transplantation. Tranilast administration was associated with a marked reduction in luminal occlusion but with no significant effect on cardiac rejection. Immunohistochemical study of the tranilast-treated graft coronary arteries revealed enhancement of p21Waf1/Cip1 and decreased expression of proliferating cell nuclear antigen in the neointima. The significant reduction in allograft vasculopathy concomitant with the enhancement of p21Waf1/Cip1 indicates that tranilast has an antiproliferative effect that could be applicable to clinical treatment of cardiac allograft vasculopathy.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Izawa

Suzuki²,

Takahashi³

et al. 2001

ATVB

View full text Add to dashboard Cite

show abstract

“…10,11 Tranilast is an orally active antiallergic agent that has been evaluated in several therapeutic areas. 12,13 Its structure and numbering scheme are as shown in Scheme 1. Several anhydrous and hydrated forms of tranilast have been previously encountered.…”

Section: Introductionmentioning

confidence: 99%

Structural analysis of polymorphism and solvation in tranilast

Vogt

Cohen

Bowman

et al. 2005

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…In addition, in some animal experiments, 200-400 mg/kg doses were used. 5,12) So the dose used in our experiment does not seem to be ridiculously high.…”

Section: Discussionmentioning

confidence: 99%

“…The decrease in Pao 2 was recovered to nearly nor- Tranilast, which was originally introduced as an anti-allergic drug, has recently attracted considerable attention because it has a variety of pharmacological actions, such as inhibition of the proliferation of fibroblasts and collagen deposition, 12) inhibition of cytokine release and production, 4,13) inhibition of angiogenesis and vascular hyper-permeability induced by vascular endothelial growth factor, 14,15) and so on. Based on these pharmacological potentials, tranilast has recently been used for the treatment of hypertrophic scars, keloids and restenosis after percutaneous transluminal coronary revascularization.…”

Section: Discussionmentioning

confidence: 99%

Preventive Effect of Tranilast on Oleic Acid-Induced Lung Injury in Guinea Pigs

Ishitsuka

Moriuchi

Chen

et al. 2004

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) are among the most severe forms of acute lung injuries with severe pulmonary edema and hypoxemia, which are seen in patients with sepsis, severe trauma, fat embolism and so on.1) The mortality of ARDS/ALI is still high (approximately 40%), despite recent advances in intensive care, because there are only a few drugs available for the prevention and treatment of ARDS/ALI. 1,2) Therefore, the development of new available drugs against ARDS/ALI is very important.In ARDS/ALI, non-cardiogenic edema develops as a result of pulmonary vascular hyper-permeability induced by inflammatory reactions. Recent studies have suggested that ARDS/ALI arises from multiple inflammatory mediators, such as cytokines, reactive oxygen species, proteases and eicosanoids, which are released from inflammatory cells (e.g. polymorphonuclear leukocytes (PMN)), possibly through complex mechanisms. 3) Tranilast (N-3,4-demethoxycinnamoyl-anthranilic acid) has been used clinically to treat allergic diseases, such as bronchial asthma, allergic rhinitis, atopic dermatitis, and hypertrophic scarring and keloid formation. Tranilast seems to have multiple anti-inflammatory effects, through inhibiting the production or releasing cytokines (e.g. tumor necrosis factor-a, interleukin-1b, and -8) or prostanoids (thromboxane A 2 and prostaglandin E 2 ) from monocytes 4) and superoxide 5) from PMNs. Nagai et al. 6) reported that tranilast ameliorated the pulmonary vascular hyper-permeability in lipopolysaccharide (LPS)-induced lung injury, one of the animal models of ARDS/ALI. Therefore, these anti-inflammatory effects of tranilast may work against ARDS/ALI caused by LPS. To extend the application of tranilast to the ARDS/ALI caused by factors other than LPS, it is necessary to examine the effects of tranilast on other animal models of acute lung injury.The injection of oleic acid (OA), an endogenous unsaturated fatty acid, can produce lung injury with pulmonary vascular hyper-permeability and hypoxemia as well as ARDS/ALI. Since pathophysiological changes induced by OA are similar to those in patients with ARDS/ALI, OA-induced lung injury is known as one of the models of these diseases.7) OA-induced lung injury resembles specific forms of ARDS/ALI that follow pancreatitis, 8) long bone fractures 9) and meconium aspiration, 10) all of which are thought to be caused by the toxicity of fatty acids. However, no research has been done to examine the effect of tranilast on lung injury induced by OA. The purpose of this study was to determine whether tranilast ameliorates pulmonary vascular hyper-permeability and hypoxemia induced by OA. MATERIALS AND METHODS AnimalsHartley strain guinea pigs (male, 650Ϯ85 g) were used. This study was approved by the Animal Care and Use Committee of Kumamoto University, and was performed in accordance with National Institutes of Health guidelines for the care and handling of animals. An operation was performed as described before. 11)Animal Treatment Animals wer...

show abstract

Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug

Cited by 28 publications

References 38 publications

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Structural analysis of polymorphism and solvation in tranilast

Preventive Effect of Tranilast on Oleic Acid-Induced Lung Injury in Guinea Pigs

Contact Info

Product

Resources

About

Tranilast: A New Application in the Cardiovascular Field as An Antiproliferative Drug

Cited by 28 publications

References 38 publications

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Structural analysis of polymorphism and solvation in tranilast

Preventive Effect of Tranilast on Oleic Acid-Induced Lung Injury in Guinea Pigs

Contact Info

Product

Resources

About

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model

Tranilast Inhibits Cardiac Allograft Vasculopathy in Association With p21 ^Waf1/Cip1 Expression on Neointimal Cells in Murine Cardiac Transplantation Model