A proteomic study of the effects of ramipril on post-infarction left ventricular remodelling in the rabbit.
OBJECTIVE
In this study, we used a proteomic approach to investigate the potential proteins regulated by ramipril in post-infarction left ventricular remodelling in the rabbit.


RESULTS
Myocardial infarction (MI) was induced in male New Zealand White rabbits (2.5-3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were either left untreated (MI group) or were treated daily for one month with 0.1 mg/kg wt of ramipril (ramipril group), then sacrificed. One month of ramipril treatment resulted in a significant improvement in the LV ejection fraction (LVEF) and a decrease in hydroxyproline content. The protein profiles of LV tissue showed that ramipril caused upregulation of glutathione peroxidase, superoxide dismutase (SOD), and heart-type fatty acid binding-protein (h-FABP) and downregulation of HSP27 and cyclophilin A. Ramipril treatment caused an increase in catalase, glutathione peroxidase, and SOD activity in the LV tissue. Oxidized glutathione levels and the GSSG/GSH ratio in the heart tissue were lower in the ramipril group than in the MI group.


CONCLUSIONS
Ramipril increased antioxidative protein expression and enzyme activity, which could partly explain the role of ramipril in attenuating LV remodelling. In addition, the present study identifies several potential protein targets which may help to explain the mechanism by which ramipril exerts its effect in post-infarction LV remodelling in the rabbit.
Chen
Ching-Yi
CY
Department of Animal Science and Technology, National Taiwan University, 50 Lane 155, Sec. 3, Keelung Rd., Taipei, Taiwan.
Lee
Bai-Chin
BC
Hsu
Hsiu-Ching
HC
Lin
Hung-Ju
HJ
Chao
Chia-Lun
CL
Lin
Yen-Hung
YH
Ho
Yi-Lwun
YL
Chen
Ming-Fong
MF
D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000032:analysis; D021984:Cyclophilin A / Q000032:analysis; D015536:Down-Regulation; D004452:Echocardiography; D015180:Electrophoresis, Gel, Two-Dimensional; D050556:Fatty Acid-Binding Proteins / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis; D006352:Heart Ventricles / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D009203:Myocardial Infarction / Q000503:physiopathology*; D011817:Rabbits; D017257:Ramipril / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013318:Stroke Volume; D013482:Superoxide Dismutase / Q000032:analysis; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000187:drug effects*
D050556:Fatty Acid-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D021984:Cyclophilin A; D017257:Ramipril; D006909:Hydroxyproline