STAT5 inhibitor attenuates atherosclerosis via inhibition of inflammation: the role of STAT5 in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease driven by lipids, which occurs preferentially in the branches or curved areas of the middle and large arteries, contributing to increased morbidity and mortality of cardiovascular disease. Recently, it has been reported that STAT5 and its regulated immune response are closely related to non-tumor diseases. However, the role of STAT5 in the development of atherosclerosis remains unknown. In this study, atherosclerosis was induced by high-fat diet (HFD) in ApoE-/- mice, and STAT5-IN-1, a STAT5 inhibitor, was orally given. Macrophages stimulated by oxLDL were used as cell models in vitro. The effects of STAT5-IN-1 in ApoE-/- mice induced by HFD were assessed, and the underlying mechanisms were investigated by siRNA-induced gene silencing. The results revealed that treatment with STAT5 inhibitor significantly attenuated atherosclerosis in ApoE-/- mice induced by HFD via decreasing inflammation. Furthermore, it was demonstrated that inhibiting STAT5 could decrease oxLDL-induced inflammation. In summary, STAT5-IN-1 may be a potential drug for the treatment of atherosclerosis, and targeting STAT5 has the ability to be a potential therapeutic strategy for reducing atherosclerosis.

Luteolin Attenuates Atherosclerosis Via Modulating Signal Transducer And Activator Of Transcription 3-Mediated Inflammatory Response.

BACKGROUND: Inflammatory factors play a crucial role throughout the development and progression of atherosclerosis, which has been considered as a chronic vascular inflammatory disease. Luteolin, a natural flavonoid which exists in many natural medicinal materials, has anti-inflammatory, anti-fibrotic and other pharmacological effects. Recently, the protective effects of luteolin on the cardiovascular disease have been reported. However, there is a paucity of studies on anti-atherosclerosis. Therefore, the anti-atherosclerosis potential of luteolin remains to be elucidated. METHOD: ApoE-/- mice were fed with a high-fat diet to induce atherosclerosis in an animal model, where they were treated with oral administration of luteolin for 12 weeks. Primary mouse peritoneal macrophages challenged with oxidized low-density lipoprotein (oxLDL) were used for in vitro mechanistic study. The effectiveness of luteolin in the ApoE-/- mouse model of atherosclerosis was estimated in the aortic sinus and enface, and the underlying mechanisms were explored by molecular modeling study and siRNA-induced gene silencing. RESULTS: Our results showed that luteolin remarkably attenuated atherosclerosis in high-fat diet-induced ApoE-/- mouse via alleviating inflammation. We further found that luteolin decreased oxLDL-induced inflammation by inhibiting signal transducer and activator of transcription 3 (STAT3) in vitro, respectively. Further molecular modeling analysis indicated that luteolin interacted with STAT3 primarily through hydrogen bond interaction. CONCLUSION: Luteolin could be a promising candidate molecule for atherosclerosis, and STAT3 may be a potential therapeutic target that could prevent the development of atherosclerosis.

Familial risk for lung cancer.

Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer.