ENDOTHELIUM‐TARGETED TRANSGENIC GTP‐CYCLOHYDROLASE I OVEREXPRESSION INHIBITS NEOINTIMA FORMATION IN MOUSE CAROTID ARTERY (English)

Clinical and Experimental Pharmacology and Physiology

Tetrahydrobiopterin (BH4) is an essential cofactor that maintains the normal function of endothelial nitric oxide (NO) synthase. Restenosis is a key complication after transluminal angioplasty. Guanosine 5′‐triphosphate‐cyclohydrolase I (GTPCH) is the first rate‐limiting enzyme for de novo BH4 synthesis. However, the role of GTPCH in restenosis is not fully understood. The present study tested the hypothesis that endothelial‐targeted GTPCH overexpression retards neointimal formation, a hallmark of restenosis, in mouse carotid artery.

Transluminal wire injury was induced in the left carotid arteries of adult male wild‐type C57BL/6 (WT) and endothelial GTPCH transgenic (Tg‐GCH) mice. Re‐endothelialization was confirmed with in vivoEvans blue staining. Endothelium‐dependent and ‐independent relaxations were measured using isometric tension recording. Morphological analysis was performed 2 and 4 weeks after carotid injury to assess neointimal formation. Fluorescence‐based high‐performance liquid chromatography (HPLC) was used to determine GTPCH activity and BH4 levels. Basal NO release following carotid injury was assessed by NG‐nitro‐l‐arginine methyl ester‐induced vascular contraction.

The endothelium was completely removed upon transluminal wire injury and full re‐endothelialization was achieved at Day 10. Endothelium‐dependent relaxation was impaired 10 days and 4 weeks after carotid injury, whereas endothelium‐independent relaxation remained unaffected. Morphological analysis revealed that the endothelial‐specific overexpression of GTPCH reduced neointimal formation and medial hypertrophy 2 and 4 weeks after carotid injury. Both arterial GTPCH enzyme activity and BH4 levels were significantly elevated in Tg‐GCH mice compared with WT mice and basal NO release of the injured carotid artery tended to increase in Tg‐GCH mice.

These findings suggest that the endothelial overexpression of GTPCH increased endothelial BH4 synthesis and played a preventive role in neointimal formation induced by endothelium denudation.

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Table of contents – Volume 34, Issue 12

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Tables of content are generated automatically and are based on records of articles contained that are available in the TIB-Portal index. Due to missing records of articles, the volume display may be incomplete, even though the whole journal is available at TIB.

1221
INVOLVEMENT OF SOMATOSTATIN RECEPTOR SUBTYPES IN MEMBRANE ION CHANNEL MODIFICATION BY SOMATOSTATIN IN PITUITARY SOMATOTROPES
Yang, Seung‐Kwon / Chen, Chen | 2007
1228
UPREGULATED ENDOTHELIN SYSTEM IN DIABETIC VASCULAR DYSFUNCTION AND EARLY RETINOPATHY IS REVERSED BY CPU0213 AND TOTAL TRITERPENE ACIDS FROM FRUCTUS CORNI
Su, Wei / Dai, De‐Zai / Liu, Hao‐Ran / Na, Tao / Dai, Yin | 2007
1234
PROTECTIVE EFFECTS OF MAGNESIUM AGAINST ISCHAEMIA–REPERFUSION INJURY THROUGH INHIBITION OF P‐SELECTIN IN RATS
Ying, Shu‐Qin / Fang, Lu / Xiang, Mei‐Xiang / Xu, Geng / Shan, Jiang / Wang, Jian‐An | 2007
1240
OATP1B1 POLYMORPHISM IS A MAJOR DETERMINANT OF SERUM BILIRUBIN LEVEL BUT NOT ASSOCIATED WITH RIFAMPICIN‐MEDIATED BILIRUBIN ELEVATION
Zhang, Wei / He, Yi‐Jing / Gan, Zhou / Fan, Lan / Li, Qing / Wang, An / Liu, Zhao‐Qian / Deng, Sheng / Huang, Yuan‐Fei / Xu, Lin‐Yong et al. | 2007
1245
RESISTANCE TO FAS‐MEDIATED APOPTOSIS IN MALIGNANT TUMOURS IS RESCUED BY KN‐93 AND CISPLATIN VIA DOWNREGULATION OF c‐FLIP EXPRESSION AND PHOSPHORYLATION
Yang, Bao‐Feng / Xiao, Chang / Li, Hong / Yang, Shi‐Jie | 2007
1252
REVERSAL OF CISPLATIN‐INDUCED CARNITINE DEFICIENCY AND ENERGY STARVATION BY PROPIONYL‐l‐CARNITINE IN RAT KIDNEY TISSUES
Aleisa, Abdulaziz M / Al‐Majed, Abdulhakeem A / Al‐Yahya, Abdulaziz A / Al‐Rejaie, Salim S / Bakheet, Saleh A / Al‐Shabanah, Othman A / Sayed‐Ahmed, Mohamed M | 2007
1260
ENDOTHELIUM‐TARGETED TRANSGENIC GTP‐CYCLOHYDROLASE I OVEREXPRESSION INHIBITS NEOINTIMA FORMATION IN MOUSE CAROTID ARTERY
Liao, Song‐Jie / Lin, Li / Zeng, Jin‐Sheng / Huang, Ru‐Xun / Channon, Keith M / Chen, Alex F | 2007
1267
INHIBITORY EFFECTS OF ENDOGENOUS l‐ARGININE ANALOGUES ON NITRIC OXIDE SYNTHESIS IN PLATELETS: ROLE IN PLATELET HYPERAGGREGABILITY IN HYPERTENSION
De Meirelles, Luisa R / Mendes‐Ribeiro, Antônio C / Santoro, Marcelle M / Mendes, Michely AP / Da Silva, Michele NSB / Mann, Giovanni E / Brunini, Tatiana MC | 2007
1272
EFFECT OF THE HEME OXYGENASE INDUCER HEMIN ON BLOOD HAEMOSTASIS MEASURED BY HIGH‐FREQUENCY ULTRASOUND
Rochefort, Gaël Y / Libgot, Rachel / Desbuards, Nicolas / Schlecht, Deborah / Halimi, Jean‐Michel / Ossant, Frederic / Eder, Veronique / Antier, Daniel | 2007
1276
Gαq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 ATTENUATES CARDIAC HYPERTROPHY IN VITROAND IN VIVO
Zhang, Hai‐Gang / Li, Xiao‐Hui / Zhou, Jian‐Zhi / Liu, Ya / Jia, Yi / Yuan, Zhi‐Bing | 2007
1276
Gaq-PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP-27 ATTENUATES CARDIAC HYPERTROPHY IN VITRO AND IN VIVO
Zhang, H. G. / Li, X. H. / Zhou, J. Z. / Liu, Y. / Jia, Y. / Yuan, Z. B. | 2007
1282
EXPRESSION OF P2X PURINOCEPTORS IN PC12 PHAEOCHROMOCYTOMA CELLS
Sun, Ji‐Hu / Cai, Guo‐Jun / Xiang, Zheng‐Hua | 2007
1287
ASSOCIATIONS BETWEEN 45T/G POLYMORPHISM OF THE ADIPONECTIN GENE AND PLASMA ADIPONECTIN LEVELS WITH TYPE 2 DIABETES
Li, Lin‐Lin / Kang, Xiao‐Long / Ran, Xin‐Jian / Wang, Ye / Wang, Chang‐Hui / Huang, Lin / Ren, Jun / Luo, Xin / Mao, Xin‐Min | 2007
1291
SYSTEMIC PLASMA LEVELS OF NITRITE/NITRATE (NOX) REFLECT BRACHIAL FLOW‐MEDIATED DILATION RESPONSES IN YOUNG MEN AND WOMEN
Casey, Darren P / Beck, Darren T / Braith, Randy W | 2007
1294
CHRONIC SUPPLEMENTATION OF CREATINE AND VITAMINS C AND E INCREASES SURVIVAL AND IMPROVES BIOCHEMICAL PARAMETERS AFTER DOXORUBICIN TREATMENT IN RATS
Santos, Ronaldo VT / Batista, Miguel L Jr / Caperuto, Érico C / Costa Rosa, Luis FBP | 2007
1300
PRESERVATION OF MECHANICAL AND ENERGETIC FUNCTION AFTER ADENOVIRAL GENE TRANSFER IN NORMAL RAT HEARTS
Sakata, Susumu / Liang, Lifan / Sakata, Naoya / Sakata, Yuri / Chemaly, Elie R / Lebeche, Djamel / Takewa, Yoshiaki / Chen, Jiqiu / Park, Woo Jin / Kawase, Yoshiaki et al. | 2007
1307
CELLULAR DISTRIBUTION OF THE RENAL BUMETANIDE‐SENSITIVE Na–K–2Cl COTRANSPORTER BSC‐1 IN THE INNER STRIPE OF THE OUTER MEDULLA DURING THE DEVELOPMENT OF HYPERTENSION IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Sonalker, Prajakta A / Tofovic, Stevan P / Jackson, Edwin K | 2007
1313
FUNCTIONAL INTERACTION BETWEEN DPI 201‐106, A DRUG THAT MIMICS CONGENITAL LONG QT SYNDROME, AND SEVOFLURANE ON THE GUINEA‐PIG CARDIAC ACTION POTENTIAL
Kang, Jiesheng / Chen, Xiao‐Liang / Reynolds, William P / Rampe, David | 2007
1317
DECREASED THRESHOLD FOR THE NITRIC OXIDE DONOR GLYCERYL TRINITRATE IN CORTISOL‐INDUCED HYPERTENSION IN HUMANS
Kelly, JJ / Tam, SH / Williamson, PM / Whitworth, JA | 2007
1319
DETECTION OF PERIVASCULAR BLOOD FLOW IN VIVO BY CONTRAST‐ENHANCED INTRACORONARY ULTRASONOGRAPHY AND IMAGE ANALYSIS: AN ANIMAL STUDY
Vavuranakis, Manolis / Papaioannou, Theodore G / Kakadiaris, Ioannis A / O'Malley, Sean M / Naghavi, Morteza / Filis, Konstantinos / Sanidas, Elias A / Papalois, Apostolos / Stamatopoulos, Ilias / Stefanadis, Christodoulos | 2007
1324
REFEREES
| 2007
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CONTENTS
| 2007

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