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The findings of recent clinical trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors produce effects beyond glucose lowering and have demonstrated beneficial cardiovascular effects that have been observed across a broad range of patients with type 2 diabetes mellitus. In particular, the cardiovascular benefit results largely from substantial and early effects of SGLT2 inhibition on cardiovascular death and hospitalization for heart failure. Recent cardiovascular outcomes trials (CVOTs) have also shown that relative risk reductions in cardiovascular outcomes were observed with SGLT2 inhibition both in patients with current and prior heart failure. Since the observed reductions of cardiovascular outcomes with SGLT2 inhibitor therapy were observed much earlier than would be expected by an anti-atherosclerotic effect, these results have led to speculation about the potential underlying pathways. Suggested mechanisms include natriuresis and osmotic diuresis; reductions in inflammation, oxidative stress, and arterial stiffness; reductions in blood pressure and body weight; and possible renoprotective effects. These effects could produce cardiovascular benefits through a range of cardiac effects, including reduction in left ventricular load, attenuation of cardiac fibrosis and inflammation, and improved myocardial energy production. Other possible mechanisms include inhibition of sodium-hydrogen exchange, increases in erythropoietin levels, and reduction in myocardial ischemia or reperfusion injury. It is likely that a range of mechanisms underlie the observed cardiovascular benefits of SGLT2 inhibitors; further elucidation of these mechanisms will be answered by ongoing research.

Bicuspid aortic valve is the most common congenital heart defect in adults. Dilatation of the proximal aorta, or bicuspid aortopathy, is present in approximately half these patients and can lead to complications, including aneurysm formation and aortic dissection. Bicuspid aortic valve is the most common congenital heart defect in adults, affecting 1.3% of the population worldwide, and is responsible for more deaths and complications than the combined effects of all the other congenital heart defects. 1 , 2 Although aortic stenosis and regurgitation are the most common complications of a bicuspid aortic valve, dilatation of any or all segments of the proximal aorta from the aortic root to the aortic arch, called bicuspid aortopathy, is also present in approximately 50% of affected persons. 1 – 4 Accumulating evidence suggests that the pattern of aortic dilatation in persons with a bicuspid aortic valve . . .

Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na+/H+ exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.

Patients with coronary artery disease were randomly assigned to either methotrexate (15 to 20 mg weekly) or placebo. At a median of 2.3 years, there was no difference between the two groups in the rate of myocardial infarction, stroke, or cardiovascular death.

Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

Main conclusionThe entire process of embryo development is under the tight control of various transcription factors. Together with other proteins, they act in a combinatorial manner and control distinct events during embryo development.Seed development is a complex process that proceeds through sequences of events regulated by the interplay of various genes, prominent among them being the transcription factors (TFs). The members of WOX, HD-ZIP III, ARF, and CUC families have a preferential role in embryonic patterning. While WOX TFs are required for initiating body axis, HD-ZIP III TFs and CUCs establish bilateral symmetry and SAM. And ARF5 performs a major role during embryonic root, ground tissue, and vasculature development. TFs such as LEC1, ABI3, FUS3, and LEC2 (LAFL) are considered the master regulators of seed maturation. Furthermore, several new TFs involved in seed storage reserves and dormancy have been identified in the last few years. Their association with those master regulators has been established in the model plant Arabidopsis. Also, using chromatin immunoprecipitation (ChIP) assay coupled with transcriptomics, genome-wide target genes of these master regulators have recently been proposed. Many seed-specific genes, including those encoding oleosins and albumins, have appeared as the direct target of LAFL. Also, several other TFs act downstream of LAFL TFs and perform their function during maturation. In this review, the function of different TFs in different phases of early embryogenesis and maturation is discussed in detail, including information about their genetic and molecular interactors and target genes. Such knowledge can further be leveraged to understand and manipulate the regulatory mechanisms involved in seed development. In addition, the genomics approaches and their utilization to identify TFs aiming to study embryo development are discussed.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor–related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor–associated DKA. Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel. DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor–associated DKA may be euglycemic (plasma glucose level <14 mmol/L). DKA is more likely in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. SGLT2 inhibitor–associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended. Preventive strategies should help avoid SGLT2 inhibitor–associated DKA. All SGLT2 inhibitor–treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol.

Patients with diabetes and recent worsening heart failure that had led to hospitalization were randomly assigned to receive sotagliflozin or placebo. At a median of 9 months, the total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure was significantly lower with sotagliflozin than with placebo.

Obesity and diabetes are strongly associated with metabolic and cardiovascular disorders including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue is identified as a complex endocrine organ, which by exerting a wide array of regulatory functions at the cellular, tissue and systemic levels can have profound effects on the cardiovascular system. Different terms including “epicardial,” “pericardial,” and “paracardial” have been used to describe adipose tissue deposits surrounding the heart. Epicardial adipose tissue (EAT) is a unique and multifaceted fat depot with local and systemic effects. The functional and anatomic proximity of EAT to the myocardium enables endocrine, paracrine, and vasocrine effects on the heart. EAT displays a large secretosome, which regulates physiological and pathophysiological processes in the heart. Perivascular adipose tissue (PVAT) secretes adipose-derived relaxing factor, which is a “cocktail” of cytokines, adipokines, microRNAs, and cellular mediators, with a potent effect on paracrine regulation of vascular tone, vascular smooth muscle cell proliferation, migration, atherosclerosis-susceptibility, and restenosis. Although there are various physiological functions of the EAT and PVAT, a phenotypic transformation can lead to a major pathogenic role in various cardiovascular diseases. The equilibrium between the physiological and pathophysiological properties of EAT is very delicate and susceptible to the influences of intrinsic and extrinsic factors. Various adipokines secreted from EAT and PVAT have a profound effect on the myocardium and coronary arteries; targeting these adipokines could be an important therapeutic approach to counteract cardiovascular disease.

This study reports the use of Genotyping-by-Sequencing (GBS) for large-scale SNP discovery and simultaneous genotyping of recombinant inbred lines (RILs) of an intra-specific mapping population of chickpea contrasting for seed traits. A total of 119,672 raw SNPs were discovered, which after stringent filtering revealed 3,977 high quality SNPs of which 39.5% were present in genic regions. Comparative analysis using physically mapped marker loci revealed a higher degree of synteny with Medicago in comparison to soybean. The SNP genotyping data was utilized to construct one of the most saturated intra-specific genetic linkage maps of chickpea having 3,363 mapped positions including 3,228 SNPs on 8 linkage groups spanning 1006.98 cM at an average inter marker distance of 0.33 cM. The map was utilized to identify 20 quantitative trait loci (QTLs) associated with seed traits accounting for phenotypic variations ranging from 9.97% to 29.71%. Analysis of the genomic sequence corresponding to five robust QTLs led to the identification of 684 putative candidate genes whose expression profiling revealed that 101 genes exhibited seed specific expression. The integrated approach utilizing the identified QTLs along with the available genome and transcriptome could serve as a platform for candidate gene identification for molecular breeding of chickpea.