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Poly (ADP-ribose) Polymerase Inhibition Improves Endothelial Dysfunction Induced by Hyperhomocysteinemia in Rats

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Abstract

Introduction

We investigated the possible protective effect of poly (ADP-ribose) polymerase (PARP) inhibition in preventing endothelial dysfunction induced by hyperhomocysteinemia (Hhcy).

Methods

Sprague–Dawley rats were divided into Hhcy group, Hhcy + 3-aminobenzamide(3-AB) group, control group and control + 3-AB group. A high-methionine diet was given to induce hyperhomocysteinemia. In Hhcy + 3-AB and control + 3-AB groups, rats were injected intraperitoneally with 3-AB (inhibitor of PARP). After 45 days, ultrastructural changes of aortas were observed by transmission electron microscope. Vascular reactivity of thoracic aortic rings was measured in organ chambers. PARP activity was detected. The levels of plasma total homocysteine, nitrite/nitrate, endothelin (ET)-1 and malondialdehyde were assayed.

Results

Rats in Hhcy group developed severe hyperhomocysteinemia and significant loss of endothelial function as measured by both vascular rings and levels of nitrite/nitrate and ET-1. Malondialdehyde levels increased significantly in Hhcy rats compared with control rats. 3-AB improved Ach-induced, NO-mediated vascular relaxation and stabilized the level of nitrite/nitrate and ET-1. Obvious improvement of ultrastructure can be observed in Hhcy + 3-AB group.

Conclusions

These results suggest that pharmacological inhibition of PARP prevents the development of endothelial dysfunction in rats with hyperhomocysteinemia which may represent a novel approach to improve vascular dysfunction associated with hyperhomocysteinemia.

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Acknowledgments

This work was supported by grants from Chenguang plan of Wuhan in China (NO:[2006] 40) and National Basic Research Program of China (973 Program): 2007CB512000;2007CB512005. We thank Professor Liu Changjing in department of physiology of Tongji Medical College for his technical assistance.

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Authors and Affiliations

  1. Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Xian Yu, Xiang Cheng, Jiang-jiao Xie, Meng-yang Liao, Rui Yao, Yong Chen, Ying-jun Ding, Ting-ting Tang & Yu-hua Liao

  2. Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430022, China

    Xiang Cheng & Yu-hua Liao

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  1. Xian Yu
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Correspondence to Xiang Cheng or Yu-hua Liao.

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Xian Yu and Xiang Cheng contribute to the work equally.

This work was supported by grants from Chenguang plan of Wuhan in China (NO:[2006] 40) and National Basic Research Program of China (973 Program): 2007CB512000;2007CB512005.

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Yu, X., Cheng, X., Xie, Jj. et al. Poly (ADP-ribose) Polymerase Inhibition Improves Endothelial Dysfunction Induced by Hyperhomocysteinemia in Rats. Cardiovasc Drugs Ther 23, 121–127 (2009). https://doi.org/10.1007/s10557-008-6146-3

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  • DOI: https://doi.org/10.1007/s10557-008-6146-3

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