Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload via regulating the crosstalk of Nrf2/ARE and TGF-β/ smads pathways in rat heart.
Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor β (TGF-β) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-β1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group. Rat models were established by incomplete constriction of abdominal aorta. After five weeks treatment, blood pressure, heart mass index (HMI), hemodynamic parameters and the average diameter of myocardium cell and collagen volume fraction (CVF) improved significantly in rosuvastatin groups, compared with the model group. Both rosuvastatin groups, increased in expression of Smad7, Nrf2, NAD (P) H dehydrogenase [quinone] 1 (Nqo1) and heme oxygenase 1(Ho1),and decreased in expression of TGF-βl、Smad3 compared with the model group. Results from co-immunoprecipitation and GST pull down showed that Nrf2 interacts with Smad7. Our results revealed the crosstalk between TGF-β1/Smads and Nrf2/ antioxidant response elements (ARE) pathways in myocardial remodeling through the interaction between Smad7 and Nrf2. Rosuvastatin can improve cardiac function and hypertrophy by regulating the crosstalk of the two signaling pathways.
['Wang|Pengbo|P|', 'Luo|Lin|L|', 'Shen|Qiusheng|Q|', 'Shi|Gaoyong|G|', 'Mohammed|Anaz|A|', 'Ni|Songshi|S|', 'Wu|Xiang|X|']
D000818:Animals D061745:Antioxidant Response Elements D001794:Blood Pressure D006332:Cardiomegaly D002460:Cell Line D049109:Cell Proliferation D003094:Collagen D006801:Humans D008297:Male D009206:Myocardium D051267:NF-E2-Related Factor 2 D051381:Rats D017207:Rats, Sprague-Dawley D000068718:Rosuvastatin Calcium D015398:Signal Transduction D051785:Smad Proteins D016212:Transforming Growth Factor beta
Rosuvastatin Nrf2 Smad Cardiac hypertrophy TGF-βl