Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.

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We conclude that this rapid-deployment valve probably facilitates minimally invasive surgery. Furthermore, a subgroup analysis showed reduced transvalvular gradients in smaller valve sizes compared with the conventionally implanted valve of the same type. The favourable haemodynamic profile and the potentially different spectrum of valve-related adverse events should be addressed in further clinical trials.

The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell–derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardiopulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell–specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell–specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.

BackgroundPrimary tumors of the heart represent an exceedingly rare entity in cardiac surgery and literature regarding management and outcome is rare. The aim of this study was to translate 15 years of experience in both multimodal diagnosis and surgical treatment of one of the largest collective of patients in literature into a detailed analysis of patient prognosis, mean survival and best treatment approach.Methods and resultsAll patients who underwent open-heart surgery at the Hospital of the Medical University of Vienna for primary cardiac tumor excision between 1999 and 2014 were analyzed retrospectively. Mean follow-up was 76.8 months. Descriptive statistical measurements were applied.113 patients were identified, 71 (62.8%) female and 42 (37.2%) male patients with a mean age of 57.9 ± 16.8 years. 90.3% (n = 102) masses were benign, 9.7% (n = 11) were malignant. Complete resection was possible for 99% and for 18.2% of benign and malignant masses, respectively. 2.9% of benign tumors and 45.5% of malignant tumors relapsed. The 30-day mortality was 1.8% (n = 2). Mean survival was 187.2 ± 2.7 months and 26.2 ± 9.8 months for benign and malignant pathologies, respectively. Sarcoma patients who underwent adjuvant combination-chemotherapy or adjuvant mono-chemotherapy and radiation had a statistically significant survival advantage of 41.5 months.ConclusionPrimary cardiac tumors remain challenging in the clinical setting. A multimodality treatment approach especially for sarcoma patients prolongs mean survival and should be regarded as the standard of care.

Transplant heart exosome profiling enables noninvasive monitoring of early acute rejection with high accuracy. Translation of this concept to clinical settings might enable development of a novel biomarker platform for allograft monitoring in transplantation diagnostics.

Objective-Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells. Approach and Results-We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites. The expression of cingulin in endothelial cells has been poorly characterized because early studies showed a low abundance of cingulin in endothelial cells when compared with epithelia. 18,19 However, the recently characterized role of GEF-H1 in regulating endothelial permeability 20,21 raises the possibility that cingulin is a key regulator of endothelial barrier function. Conclusions-WeHere, we studied the expression and molecular environment of cingulin in different types of endothelial cells. Furthermore, we characterized the effects of exogenous cingulin expression or deletion of the cingulin head domain on the expression of claudin-5 and endothelial barrier function and analyzed barrier function in cingulin-deficient mice. The results indicate that expression levels of cingulin contribute to regulating endothelial barrier function. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement. Results Cingulin Is Localized at Human Endothelial TJ In SituWe analyzed the expression of cingulin in different vascular beds by immunohistochemistry. Endothelial cells of large and small-sized veins and arteries in human skin, lung, and brain tissues stained positive with anticingulin antibodies ( Figure 1A). By immunofluorescence, cingulin labeling was detected in close proximity of VE-cadherin labeling with a Pearson correlation coefficient of 0.11, but was colocalizing with ZO-1 labeling resulting in a Pearson correlation coefficient of 0.31 ( Figure 1B), supporting the notion that cingulin is associated with TJ of endothelial cells. 22 Analysis of mRNA expression levels of cingulin relative to VE-cadherin in different tissues and vessels showed that cingulin expression was detectable in the brain, the vena cava, and the aorta, whereas no expression was detected in muscle an...

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