The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

神经保护剂甲磺酸雷沙吉兰可减轻实验性心肌梗死后的心脏重塑

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作者:Aimilia Varela, Manolis Mavroidis, Michalis Katsimpoulas, Irini Sfiroera, Niki Kappa, Angelica Mesa, Nikolaos G Kostomitsopoulos, Dennis V Cokkinos

Aim

Rasagiline mesylate (N-propargyl-1 (R)-aminoindan) (RG) is a selective, potent irreversible inhibitor of monoamine oxidase-B with cardioprotective and anti-apoptotic properties. We investigated whether it could be cardioprotective in a rat model undergoing experimental myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery.

Conclusions

Our study demonstrates a positive effect of RG in the post-MI period with a significant attenuation in cardiac remodelling.

Results

RG was administered, intraperitoneally, for 28 days (2 mg/kg) starting 24 h after MI induction. Echocardiography analysis revealed a significant reduction in left ventricular end-systolic and diastolic dimensions and preserved fractional shortening in RG-treated compared with normal saline group at 28 days post-MI (31.6 ± 2.3 vs. 19.6 ± 1.8, P < 0.0001), respectively. Treatment with RG prevented tissue fibrosis as indicated by interstitial collagen estimation by immunofluorescence staining and hydroxyproline content and attenuated the number of apoptotic myocytes in the border zone (65%) as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Caspase 3 relative protein levels were significantly decreased in the non-infarcted myocardium. Markedly decreased malondialdehyde levels in the border zone indicate a reduction in tissue oxidative stress. Conclusions: Our study demonstrates a positive effect of RG in the post-MI period with a significant attenuation in cardiac remodelling.

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