Thioredoxin-1 gene delivery induces heme oxygenase-1 mediated myocardial preservation after chronic infarction in hypertensive rats

Abstract

Background: Hypertension, the major risk factor for many cardiovascular diseases, is a result of multiple causes along with excessive generation of reactive oxygen species (ROS) resulting in imbalance of redox status. Methods: In this study, we investigated the therapeutic potential of Adenoviral- Thioredoxin-1 (Adeno-Trx-1) in spontaneous hypertensive rats (SHRs) at a dosage of 1 × 109 pfu. The rats were assigned as normotensive Wistar-Kyoto (WKY), SHR, SHR + Adeno-Lac-Z (SHRLac-Z), and SHR + Adeno-Trx-1 (SHRTrx-1). Echo-guided injection of adeno virus was done 48 h before permanent myocardial infarction (MI) by left anterior descending coronary artery (LAD) occlusion. Results: Decreased infarct size (52 ± 4.1% vs. 67 ± 6.1%), number of apoptotic cardiomyocytes (161 ± 14.8 vs. 240 ± 22.2), left ventricular inner diameter (7 ± 0.33 vs. 9 ± 0.46 mm), increased ejection fraction (52 ± 6.3 vs. 42 ± 3.3%), and fractional shortening (28 ± 1.8 vs. 22 ± 2.04 %) was observed in the SHRTrx-1 compared to SHR. Western Blot and immunohistochemical analysis demonstrated increased expression of Trx-1, HO-1, and Bcl-2 in the SHRTrx-1 compared to SHR. In addition, increased HO-1 activity was also observed in SHRTrx-1 as compared to SHR and SHRLac-Z groups. Conclusion: Our study demonstrates that the cardioprotective effect of Adeno-Trx-1 gene therapy in SHR is Trx-1/HO-1/Bcl-2 mediated and may represent future target to develop therapy against hypertension associated cardiac failure. © 2009 American Journal of Hypertension, Ltd.