YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9

Yi Nan Liu, Shiow Lin Pan, Chieh Yu Peng, Jih Hwa Guh, Dong Ming Huang, Ya Ling Chang, Chun Hung Lin, Hui Chen Pai, Sheng Chu Kuo, Fang Yu Lee, Che Ming Teng

研究成果: 雜誌貢獻文章

38 引文 (Scopus)

摘要

Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and postrevascularization production of vascular smooth muscle cells may play key roles in development of arterial restenosis. We investigated the inhibitory effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a benzyl indazole compound, on MMP-2 and MMP-9 activity in a balloon-injury rat carotid artery model. Injury was induced by inserting a balloon catheter through the common carotid artery; after 14 days, histopathological analysis using immunostaining and Western blotting revealed significant restenosis with neointimal formation that was associated with enhanced protein expression of MMP-2 and MMP-9. However, these effects were dose-dependently reduced by orally administered YC-1 (1-10 mg/kg). In addition, gelatin zymography demonstrated that increased MMP-2 and MMP-9 activity was diminished by YC-1 treatment. On the other hand, YC-1 inhibited hydrolysis of the fluorogenic quenching substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by recombinant MMP-2 and MMP-9 with IC50 values = 2.07 and 8.20 μM, respectively. Reverse transcription-polymerase chain reaction analysis of MMP-2 and MMP-9 mRNA revealed that YC-1 significantly inhibited mRNA levels of MMPs. Finally, for the YC-1 treatment group, we did not observe elevation of cGMP levels using enzyme-linked immunosorbent assay, suggesting that YC-1 inhibition of neointimal formation is not through a cGMP-elevating pathway. These data show YC-1 suppression of neointimal formation is dependent on its influence on MMP-2 and MMP-9 protein, mRNA expression, and activity, but not through a cGMP-elevating effect. YC-1 shows therapeutic potential for treatment of restenosis after angioplasty.
原文英語
頁(從 - 到)35-41
頁數7
期刊Journal of Pharmacology and Experimental Therapeutics
316
發行號1
DOIs
出版狀態已發佈 - 一月 2006
對外發佈Yes

指紋

Indazoles
Neointima
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Messenger RNA
Benzyl Compounds
Carotid Artery Injuries
Common Carotid Artery
Gelatin
Therapeutics
Fluorescent Dyes
Vascular Smooth Muscle
Angioplasty
Inhibitory Concentration 50
Reverse Transcription
Smooth Muscle Myocytes
Proteins
Hydrolysis
Catheters

ASJC Scopus subject areas

  • Pharmacology

引用此文

YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9. / Liu, Yi Nan; Pan, Shiow Lin; Peng, Chieh Yu; Guh, Jih Hwa; Huang, Dong Ming; Chang, Ya Ling; Lin, Chun Hung; Pai, Hui Chen; Kuo, Sheng Chu; Lee, Fang Yu; Teng, Che Ming.

於: Journal of Pharmacology and Experimental Therapeutics, 卷 316, 編號 1, 01.2006, p. 35-41.

研究成果: 雜誌貢獻文章

Liu, Yi Nan ; Pan, Shiow Lin ; Peng, Chieh Yu ; Guh, Jih Hwa ; Huang, Dong Ming ; Chang, Ya Ling ; Lin, Chun Hung ; Pai, Hui Chen ; Kuo, Sheng Chu ; Lee, Fang Yu ; Teng, Che Ming. / YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9. 於: Journal of Pharmacology and Experimental Therapeutics. 2006 ; 卷 316, 編號 1. 頁 35-41.
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abstract = "Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and postrevascularization production of vascular smooth muscle cells may play key roles in development of arterial restenosis. We investigated the inhibitory effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a benzyl indazole compound, on MMP-2 and MMP-9 activity in a balloon-injury rat carotid artery model. Injury was induced by inserting a balloon catheter through the common carotid artery; after 14 days, histopathological analysis using immunostaining and Western blotting revealed significant restenosis with neointimal formation that was associated with enhanced protein expression of MMP-2 and MMP-9. However, these effects were dose-dependently reduced by orally administered YC-1 (1-10 mg/kg). In addition, gelatin zymography demonstrated that increased MMP-2 and MMP-9 activity was diminished by YC-1 treatment. On the other hand, YC-1 inhibited hydrolysis of the fluorogenic quenching substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 by recombinant MMP-2 and MMP-9 with IC50 values = 2.07 and 8.20 μM, respectively. Reverse transcription-polymerase chain reaction analysis of MMP-2 and MMP-9 mRNA revealed that YC-1 significantly inhibited mRNA levels of MMPs. Finally, for the YC-1 treatment group, we did not observe elevation of cGMP levels using enzyme-linked immunosorbent assay, suggesting that YC-1 inhibition of neointimal formation is not through a cGMP-elevating pathway. These data show YC-1 suppression of neointimal formation is dependent on its influence on MMP-2 and MMP-9 protein, mRNA expression, and activity, but not through a cGMP-elevating effect. YC-1 shows therapeutic potential for treatment of restenosis after angioplasty.",
author = "Liu, {Yi Nan} and Pan, {Shiow Lin} and Peng, {Chieh Yu} and Guh, {Jih Hwa} and Huang, {Dong Ming} and Chang, {Ya Ling} and Lin, {Chun Hung} and Pai, {Hui Chen} and Kuo, {Sheng Chu} and Lee, {Fang Yu} and Teng, {Che Ming}",
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T1 - YC-1 [3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9

AU - Liu, Yi Nan

AU - Pan, Shiow Lin

AU - Peng, Chieh Yu

AU - Guh, Jih Hwa

AU - Huang, Dong Ming

AU - Chang, Ya Ling

AU - Lin, Chun Hung

AU - Pai, Hui Chen

AU - Kuo, Sheng Chu

AU - Lee, Fang Yu

AU - Teng, Che Ming

PY - 2006/1

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