Resistin, originally described as an adipocyte‐specific hormone, has been suggested to be an important link between obesity, insulin resistance and diabetes. Although its expression was initially defined in adipocytes, significant levels of resistin expression in humans are mainly found in mononuclear leukocytes, macrophages, spleen and bone marrow cells. Increasing evidence indicates that resistin plays important regulatory roles apart from its role in insulin resistance and diabetes in a variety of biological processes: atherosclerosis and cardiovascular disease (CVD), non‐alcoholic fatty liver disease, autoimmune disease, malignancy, asthma, inflammatory bowel disease and chronic kidney disease. As CVD accounts for a significant amount of morbidity and mortality in patients with diabetes and without diabetes, it is important to understand the role that adipokines such as resistin play in the cardiovascular system. Evidence suggests that resistin is involved in pathological processes leading to CVD including inflammation, endothelial dysfunction, thrombosis, angiogenesis and smooth muscle cell dysfunction. The modes of action and signalling pathways whereby resistin interacts with its target cells are beginning to be understood. In this review, the current knowledge about the functions and pathophysiological implications of resistin in CVD development is summarized; clinical translations, therapeutic considerations and future directions in the field of resistin research are discussed. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3

The discovery of microRNAs (miRNAs) represents one of the most significant advances in biological and medical sciences in the last decade. Hundreds of miRNAs have been identified in plants, viruses, animals and human beings, and these tiny, non-coding RNA transcripts have been found to play crucial roles in important biological processes involved in human health and disease. Recently, many studies have demonstrated that miR-196 plays critical roles in normal development and in the pathogenesis of human disease processes such as cancer. Several investigations have implemented cell culture and animal models to explore the potential molecular mechanisms of miR-196. This review provides updated information about the structure of the miR-196 gene and the roles of miR-196 in development, cancer and disease formation. Importantly, we discuss the possible molecular mechanisms whereby miR-196 regulates cellular functions including targeting molecules and gene regulation pathways; potential clinical applications are addressed, as well as future directions for investigation. miR-196a may prove to be a novel therapeutic target for several cancers.

Background X inactive-specific transcript (XIST) RNA is involved in X chromosome silencing in female cells and allows X chromosome equilibration with males. X inactive-specific transcript expression has been found to be dysregulated in a variety of human cancers when compared to normal cells; meanwhile, the inactivated X chromosome has been noted to be conspicuously absent in human cancer specimens, whereas X chromosome duplications are widely noted. The specific pathways whereby changes in X chromosome status and XIST expression occur in cancer remain incompletely described. Nevertheless, a role for XIST in BRCA1-mediated epigenetic activity has been proposed. Methods Here we review the data regarding XIST expression and X chromosome status in a variety of female, male, and non–sex-related human cancers. Conclusions It is not yet known whether X chromosome duplication, XIST dysregulation, and over-expression of X-linked genes represent important factors in tumorgenesis or are simply a consequence of overall epigenetic instability in these cancers.

Acute massive pulmonary embolism (PE) is a life-threatening condition that requires prompt and aggressive interventions, includinganticoagulation, catheter-directed thrombolysis (CDT), mechanical thrombectomy, or surgical thromboembolectomy. The aim of this study was to evaluate the treatment outcome in patients with massive PE who were treated with either ultrasound-accelerated thrombolysis using the EkoSonic Endovascular System (EKOS) or CDT intervention. During a recent 10-year period, the clinical records of all patients with massive PE undergoing catheter-directed interventions were evaluated. Patients were divided into two treatment groups: EKOS versus CDT interventions. Comparisons were made with regard to the treatment outcome between the two groups. Twenty-five patients underwent 33 catheter-directed interventions for massive PE during the study period. Among them, EKOS or CDT was performed in 15 (45%) and 18 (55%) procedures, respectively. In the EKOS group, complete thrombus removal was achieved in 100% cases. In the CDT cohort, complete or partial thrombus removal was accomplished in 7 (50%) and 2 (14%) cases, respectively. Comparing treatment success based on thrombus removal, EKOS treatment resulted in an improved treatment outcome compared with the CDT group (p < .02). The mean time of thrombolysis in EKOSand CDT group was 17.4 ± 5.23 and 25.3 ± 7.35 hours, respectively (p = .03). The mortality rate in the EKOS and CDT group was 9.1% and 14.2%, respectively (not significant). Treatment-related hemorrhagic complication rates in the EKOS and CDT group were 0% and 21.4%, respectively (p = .02). A significant reduction in Miller scores was noted in both groups following catheter-based interventions. No significant difference in relative Miller score improvement was observed between groups. Ultrasound-accelerated thrombolysis using the EkoSonic system is an effective treatment modality in patients with acute massive PE. When compared with CDT, this treatment modality provides similar treatment efficacy with reduced thrombolytic infusion time and treatment-related complications.

AbstractmiRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease. Keywordsatherosclerosis; biomarker; lipoprotein metabolism; miRNA; therapeutic target; vascular disease; vascular smooth muscle cell The cardiovascular system is composed of the heart, blood vessels and blood. It is connected intimately with every other organ system, and dysfunction of the cardiovascular system can have devastating downstream effects. The lumen of blood vessels is lined by a monolayer of endothelial cells, which forms the main physical barrier between the blood and vessel wall, controlling the movement of solutes and fluid from the vascular space to the surrounding tissues [1]. Endothelial dysfunction owing to breakdown of the endothelial cell-cell barrier can promote atherogenesis through the increased adherence of leukocytes, monocytes and macrophages, and subendothelial accumulation of cholesterol-bearing lipoproteins [2,3]. Meanwhile, vascular smooth muscle cells (VSMCs) below the endothelium undergo phenotypic modulation from a contractile phenotype to a proliferative state under the influence of mechanical stress, growth factors, inflammatory mediators, such as low-density lipoprotein (LDL) deposition, and leukocyte or monocyte infiltration [4]. Aberrant