Atorvastatin attenuates cardiac hypertrophy through AMPK/miR-143-3p/Bcl2 axis.

Atorvastatin is employed as a lipid lowering agent and its heart protective effect has been recently reported as well. However, the mechanism of atorvastatin in attenuating cardiac hypertrophy and inhibiting cardiac failure is unclear. In our study, cardiac hypertrophy was induced in rats using transverse aortic constriction (TAC) method and in cardiomyocytes using angiotensin II (Ang II). Atorvastatin significantly suppressed TAC-induced heart weight increase and cardiomyocytes apoptosis in rats. At a molecular level, we found that miR-143-3p was significantly up-regulated, and the up-regulation could be inhibited by atorvastatin via activating AMPK pathway. Furthermore, it was validated that Bcl2 was one of the target genes of miR-143-3p. Taken together, the data indicated that miR-143-3p aggravated cardiac hypertrophy by inducing cardiomyocytes apoptosis through inhibiting Bcl2 expression. This study demonstrated the effects of atorvastatin in attenuating cardiac hypertrophy and inhibiting cardiac failure, which is depending on Bcl2 expression via miR-143-3p inhibition by AMPK activation.

Galectin-3 mediates high-glucose-induced cardiomyocyte injury by the NADPH oxidase/reactive oxygen species pathway.

Galectin-3 is a member of the ß-galactoside-binding lectin family taking part in the regulation of inflammation, angiogenesis, and fibrosis. This study was designed to study the improved effect of galectin-3 inhibition on diabetic cardiomyopathy (DCM). Sprague-Dawley rats were randomized into the control, DCM, and DCM + modified citrus pectin (MCP) (a galectin-3 pharmacological inhibitor) groups. After 8 weeks, streptozotocin-induced DCM led to high blood glucose level, oxidative stress, cardiac injury, and dysfunction accompanied by suppressed body mass. On the contrary, MCP (100 mg·kg-1·day-1) administration improved body mass and blood glucose level and attenuated cardiac injury and dysfunction in DCM rats. Additionally, MCP attenuated pathological changes in plasma and myocardial tissue markers of oxidative stress, such as hydrogen peroxide and malonyldialdehyde, although it did not change superoxide dismutase activities, which were decreased in the DCM group. The levels of oxidative stress associated proteins evaluated by Western blot, such as p67phox and NADPH oxidase 4, were obviously increased in the DCM group, while they were reversed by MCP treatment. Therefore, galectin-3-mediated high-glucose-induced cardiomyocyte injury and galectin-3 inhibition attenuated DCM by suppressing NADPH oxidase. These findings suggested that galectin-3 could be a potential target for treatment of patients with DCM.

Circ_RUSC2 upregulates the expression of miR-661 target gene SYK and regulates the function of vascular smooth muscle cells.

Many studies have identified circRNA as a prospective direction in the field of cardiovascular research. Detection of circRNA expression in different vascular smooth muscle cell (VSMC) phenotypes revealed that circ_RUSC2 is upregulated in proliferative VSMCs. Sequence analysis of circ_RUSC2 showed that there are multiple binding sites of miR-661 on circ_RUSC2, and that SYK is an important target gene of miR-661. MiR-661 expression is downregulated in proliferative VSMCs, whereas the expression of SYK is upregulated. Circ_RUSC2 and miR-661 do not affect each other's expression levels, but circ_RUSC2 can promote the expression of SYK and inhibit the expression of SM22-alpha, whereas miR-661 has the opposite effect. At the same time, VSMC proliferation and migration can be promoted by SYK or circ_RUSC2, but the linear sequence of circ_RUSC2 can not. MiR-661 and circ_RUSC2 siRNAs inhibit VSMC proliferation and migration, and promote cell apoptosis. When an miR-661 mimic or SYK siRNAs were co-transfected with circ_RUSC2 overexpression vector, VSMC proliferation, apoptosis, and migration were not significantly altered. Accordingly, circ_RUSC2 can promote the expression of SYK, a target gene of miR-661, and regulate VSMC proliferation, apoptosis, phenotypic modulation, and migration. These findings will supply a theoretical basis for studying circRNA function in VSMCs, and new ideas for the diagnosis and treatment of cardiovascular diseases.

LncRNA SRA deregulation contributes to the development of atherosclerosis by causing dysfunction of endothelial cells through repressing the expression of adipose triglyceride lipase.

It has been well established that long non­coding RNAs (lncRNAs) are crucial mediators in a diverse range of diseases, including atherosclerosis. The present study aimed to examine the molecular mechanisms underlying the association between steroid receptor RNA activator (SRA) and atherosclerosis. Reverse transcription­quantitative polymerase chain reaction analysis, western blot analysis and luciferase assays were performed to examine interactions among SRA, adipose triglyceride lipase (ATGL) and peroxisome proliferator­activated receptor (PPARγ), and the effect of resveratrol (RSV) on the levels of SRA, ATGL and PPARγ. ELISA was performed to determine the effects of SRA and RSV on the production of inflammatory­associated cytokines. The results showed that knockdown of the expression of SRA by transfecting HUVECs with short hairpin RNA­SRA inhibited the production of ATGL and PPARγ. A plasmid coding SRA RNA, but not the SRAP protein, attenuated the luciferase activity of the ATGL promoter. PPARγ had no effect on the luciferase activity driven by the ATGL promoter in the absence of rosiglitazone, whereas the luciferase activity of the ATGL promoter was elevated in the presence of rosiglitazone. This effect was eliminated by SRA. SRA enhanced the production of inflammatory­associated cytokines, including tumor necrosis factor­α, interleukin­6, monocyte chemotactic protein­1 and intercellular adhesion molecule­1; however, the promoting effect of SRA was eliminated by RSV. RSV increased the expression of ATGL and PPARγ, but not that of SRA. RSV distinctly and concentration­dependently upregulated the luciferase activity of ATGL, compared with that in the cells without RSV treatment, whereas treating with rosiglitazone inhibited the effect of RSV on the luciferase activity of ATGL. The present study examined the roles of SRA in atherosclerosis, and the effects of changes in SRA and ATGL on inflammatory cytokines and HUVEC dysfunction.

Saliency region detection based on Markov absorption probabilities.

In this paper, we present a novel bottom-up salient object detection approach by exploiting the relationship between the saliency detection and the Markov absorption probability. First, we calculate a preliminary saliency map by the Markov absorption probability on a weighted graph via partial image borders as background prior. Unlike most of the existing background prior-based methods which treated all image boundaries as background, we only use the left and top sides as background for simplicity. The saliency of each element is defined as the sum of the corresponding absorption probability by several left and top virtual boundary nodes, which are most similar to it. Second, a better result is obtained by ranking the relevance of the image elements with foreground cues extracted from the preliminary saliency map, which can effectively emphasize the objects against the background, whose computation is processed similarly as that in the first stage and yet substantially different from the former one. At last, three optimization techniques--content-based diffusion mechanism, superpixelwise depression function, and guided filter--are utilized to further modify the saliency map generalized at the second stage, which is proved to be effective and complementary to each other. Both qualitative and quantitative evaluations on four publicly available benchmark data sets demonstrate the robustness and efficiency of the proposed method against 17 state-of-the-art methods.