Cardiovascular Drugs and Therapy

, Volume 23, Issue 2, pp 121–127

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

Authors

  • Xian Yu
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union HospitalHuazhong University of Science and Technology
  • Jiang-jiao Xie
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
  • Meng-yang Liao
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
  • Rui Yao
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
  • Yong Chen
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
  • Ying-jun Ding
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
  • Ting-ting Tang
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and Technology
    • Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union HospitalHuazhong University of Science and Technology
Article

DOI: 10.1007/s10557-008-6146-3

Cite this article as:
Yu, X., Cheng, X., Xie, J. et al. Cardiovasc Drugs Ther (2009) 23: 121. doi:10.1007/s10557-008-6146-3

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.

Key words

HyperhomocysteinemiaPoly(ADP-ribose) polymeraseEndothelial dysfunction3-AminobenzamideOxidative stress

Copyright information

© Springer Science+Business Media, LLC 2008