Rationale: Endothelial dysfunction is an important determinant risk factor for the development of hypertension and its complications. Thus, identification of potential therapeutic targets for preventing endothelial dysfunction has major clinical importance. Emerging evidence indicates that epigenetic modifications are closely associated with the regulation of endothelial function. Among them, HDAC (histone deacetylase)-mediated epigenetic processes in vascular homeostasis and cardiovascular disease have attracted much attention. SIRT6 (sirtuin 6) is one member of SIRTs (class III HDAC) that are highly conserved NAD + -dependent deacetylases. Objective: This study was designed to elucidate the role of SIRT6 in the pathogenesis of hypertension, discover the new targets of SIRT6, and explore related mechanisms on the regulation of endothelial function. Methods and Results: The levels of endothelial SIRT6 were significantly reduced in 2 independent hypertension models: desoxycorticosterone acetate/salt–induced and Ang II (angiotensin II)–induced hypertensive mice. Utilizing genetically engineered endothelial-specific SIRT6 knockout (Cre + /SIRT6 fl/fl ) mice, we found that endothelial-specific deletion of SIRT6 significantly enhanced blood pressure, exacerbated endothelial dysfunction and cardiorenal injury in experimental hypertension. Functionally, SIRT6 has pleiotropic protective actions in endothelial cells, which include promoting endothelium-dependent vasodilatation and vascular NO bioavailability, reducing cellular permeability, ameliorating endothelial senescence and apoptosis, and facilitating autophagy. Mechanistically, SIRT6 induced the expression of GATA5 (GATA-binding protein 5), a novel regulator of blood pressure, through inhibiting Nkx3.2 (NK3 homeobox 2) transcription by deacetylating histone H3K9 (histone H3 lysine 9), thereby regulating GATA5-mediated signaling pathways to prevent endothelial injury. Finally, we provide direct evidence for the therapeutic potential of SIRT6 in desoxycorticosterone acetate/salt–induced hypertensive mice by overexpression of SIRT6 in vivo. Conclusions: This study for the first time demonstrates that SIRT6 prevents hypertension and its complications by maintaining endothelial function. Pharmacological targeting of SIRT6 may be an innovative therapeutic strategy for treating patients with hypertension.

These findings indicate that serum miR-221 may have a role as a novel diagnostic and prognostic marker, and may have potential as a therapeutic target in EOC.

Objectives: is downregulated in many human malignancies, which correlates with tumour progression. This study characterized the contribution of miR-206 to the initiation and progression of human breast cancer. Methods: Consecutive primary breast cancer patients who received radical resection were enrolled. Breast cancer tissue samples were obtained during surgery. MiR-206 levels in matched pairs of cancer tissue and normal adjacent tissue (NAT) samples were examined using quantitative reverse transcription-polymerase chain reaction. The relationship between miR-206 levels and clinicopathological characteristics and overall survival was also investigated. Results: In 128 patients with breast cancer, miR-206 was downregulated in 119 (93%) tumour tissue compared with their matched NAT samples. Decreased miR-206 was significantly associated with advanced clinical stage and lymph node metastasis. Univariate and multivariate Cox proportional hazard regression analysis revealed that a low miR-206 level was an unfavourable prognostic factor for overall survival, in patients with breast cancer. Conclusions: This study indicated that miR-206 may be a good candidate as a novel prognostic indicator in breast cancer patients.

Objectives: To detect microRNA (miR)-126 expression and its correlation with vascular endothelial growth factor (VEGF) levels in placentas from patients with pre-eclampsia compared with those from normotensive pregnancies. Methods: miR-126 expression, and VEGF mRNA and protein levels, in placentas collected sequentially from patients with pre-eclampsia and normotensive pregnancies were measured using real-time reverse transcription-polymerase chain reaction and Western blot, respectively. The relationship between miR-126 and VEGF expression was analysed statistically. The regulatory effect of miR-126 on VEGF expression in human placental choriocarcinoma (BeWo) cells in vitro was also investigated. Results: miR-126 expression was decreased, and VEGF mRNA and protein levels were significantly lower, in placentas from patients with pre-eclampsia (n ¼ 115) compared with placentas from normotensive pregnancies (n ¼ 115). A positive correlation was found between VEGF mRNA and miR-126 expression (r ¼ 0.79). In addition, miR-126 overexpression significantly upregulated VEGF expression in BeWo cells, whereas miR-126 downregulation decreased VEGF expression. Conclusions: miR-126 was downregulated in placentas from patients with pre-eclampsia and this correlated with decreased VEGF expression. These findings indicate that miRNA-126 may be involved in pre-eclampsia pathogenesis and could be a potential biomarker for this disease.

Application of preoperative transfemoral abdominal aorta balloon occlusion during cesarean section is a safe and effective strategy for patients with placenta increta and/or percreta. It could reduce intraoperative blood loss and enhance the possibility of uterus preservation and ensure the safety of life from severe complications.