Rosuvastatin improves myocardial hypertrophy after hemodynamic pressure overload via regulating the crosstalk of Nrf2/ARE and TGF-ß/ smads pathways in rat heart.

Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor ß (TGF-ß) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-ß1 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-ßl、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-ß1/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.

Panax notoginseng saponins reduce high-risk factors for thrombosis through peroxisome proliferator-activated receptor -γ pathway.

The classic Virchow theory suggests that blood stasis, hypercoagulability and endothelial dysfunction are three major factors that cause venous thrombosis (VT). It is a complicated biological process involved multi-factors. Platelet plays a central role and participates in multiple links of this process. Panax notoginseng saponins (PNS), the principal constituents derived from panax notoginseng, has been widely described for its anti-platelet activity. However, its potential mechanism against platelet aggregation has not been clarified. In this present study, we evaluated the anti-platelet effects of PNS on thrombin-induced platelet activation and its possible molecular mechanism of action, and further explored the therapeutic action of PNS on thrombin induced hypercoagulability in rat. Our results showed that PNS treatment inhibited platelet aggregation induced by thrombin, which was accompanied with over-expression of Peroxisome proliferator-activated receptor γ (PPAR-γ) protein, mRNA and upregulation of phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (Akt)/ endothelial nitric oxide synthase (eNOS) pathway in platelet, and this effect could be reversed by PPAR-γ inhibitor T0070907. In vivo, PNS significantly reversed thrombin-induced hypercoagulable state in rat which was accompanied by PPAR-γ protein and mRNA upregulation in rat lung. In conclusion, these data suggested that PNS could suppress thrombin-induced platelet aggregation in vitro and effectively improve hypercoagulable state in vivo and PNS-induced activation of PPAR-γ and its downstream PI3K/Akt/eNOS pathway played the central role.