| Yeong-Shin Lee1, Myeong-Chan Cho1, Kyung-Kuk Hwang1 , Ki-Seok Kim2 , Ju-hee Son1, Jin-Sook Kwon1, Jang-Whan Bae1, Dong-Woon Kim1, |
Backgrounds and Objective:Reactive oxygen species participate in signal transduction during cellular growth and differentiation. Although cellular redox balance may play an important role in cardiac hypertrophy and its regression, mechanisms of regulation of redox are incompletely defined. We analyzed the redox status, expression of redox regulating protein, thioredoxin(Trx) in heart from pressure overload-induced cardiac hypertrophy, and the change of Trx expression during regression of cardiac hypertrophy. Design and Methods:Pressure overaload-induced cardiac hypertrophy was obtained by controlled constriction of transverse aorta(TAC) of Spraque-Dawley rat. Dynamic expression of Trx, thioredoxin-interacting protein(Txnip), endogenous inhibitor of Trx, and thioredoxin reductase(TrxR) were evaluated by Western blot in heart from cardiac hypertrophy by TAC(1,3,5days,1,2weeks;n=10, 2/each time point) and regression by relieving constriction(serial time points of 1,3,5days,1,2weeks;n=10, 2/each time point). Hemodynamic measurement were evaluated by P-50 tube. The weight of extracted heart was measured. Results: Systolic blood pressure of TAC group was significantly increased after immediate consriction and persisted upto 2weeks(195.0±5.0 vs 110.9±10.2mmHg, p<0.01). Anatomical change of LV hypertrophy in TAC group was observed at 2weeks(septal wall thickness: 1.94±0.38 vs 1.28±0.13mm,p<0.05, LV mass/body weigh: 2.69±0.31 vs 2.26±0.28mg/g,p<0.05). Expression of Trx/Txnip ratio was significantly increased from D1 till D3(acute hypertensive stress period) and then decreased till 2 weeks(relatively adapted period). Expression of TrxR was more increased in TAC group till 1week. Significant decrease of blood pressure(151.1±21.5 vs 117.2±20.1mmHg,p<0.01) at relieving TAC and regression of LVH was observed at 3days later(LV mass/body weight; 2.69±0.31 vs 2.12±0.37mg/g, p<0.05). Immediately after relieving of constriction, the expression pattern of Trx, Txnip were reversed from D1(untying TAC). Theses findings suggest dynamic role of Trx, Txnip and TrxR in hypertension and LVH. Conclusion: Trx system including Trx, Txnip and TrxR may play a crucial role in the development and regression of hypertension and LVH.
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