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 x 10(9) 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.
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 hypertensiverats (SHRs) at a dosage of 1 x 10(9) 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.
Authors: Alexey A Tinkov; Geir Bjørklund; Anatoly V Skalny; Arne Holmgren; Margarita G Skalnaya; Salvatore Chirumbolo; Jan Aaseth Journal: Cell Mol Life Sci Date: 2018-01-11 Impact factor: 9.261
Authors: Gwen Lagoda; Yi Xie; Sena F Sezen; K Joseph Hurt; Limin Liu; Biljana Musicki; Arthur L Burnett Journal: J Sex Med Date: 2011-10-13 Impact factor: 3.802
Authors: Julio Madrigal-Matute; Roxana Martinez-Pinna; Carlos Ernesto Fernandez-Garcia; Priscila Ramos-Mozo; Elena Burillo; Jesus Egido; Luis Miguel Blanco-Colio; Jose Luis Martin-Ventura Journal: Oxid Med Cell Longev Date: 2012-06-25 Impact factor: 6.543