New vessel formation in the context of cardiomyocyte regeneration – the role and importance of an adequate perfusing vasculature

The history of revascularization for cardiac ischemia dates back to the early 1960’s when the first coronary artery bypass graft procedures were performed in humans. With this 50 year history of providing a new vasculature to ischemic and hibernating myocardium, a profound depth of experience has been amassed in clinical cardiovascular medicine as to what does, and does not work in the context of cardiac revascularization, alleviating ischemia and adequacy of myocardial perfusion. These issues are of central relevance to contemporary cell-based cardiac regenerative approaches. While the cardiovascular cell therapy field is surging forward on many exciting fronts, several well accepted clinical axioms related to the cardiac arterial supply appear to be almost overlooked by some of our current basic conceptual and experimental cell therapy paradigms. We present here information drawn from five decades of the clinical revascularization experience, review relevant new data on vascular formation via cell therapy, and put forward the case that for optimal cell-based cardiac regeneration due attention must be paid to providing an adequate vascular supply

Cutaneous Vasculitis and Central Nervous System Infarctions due to Varicella Zoster Virus Vasculopathy in an Immunocompromised Patient

Varicella zoster virus (VZV) infection commonly presents as varicella during childhood, and zoster, later in life. Here, we present a rare and interesting case of VZV infection that manifested with both cerebral and spinal infarctions and cutaneous vasculitis in the absence of a classic vesicular rash in an immunocompromised patient

Estimation of right atrial and ventricular hemodynamics by CT coronary angiography.

BACKGROUND: Computed tomography coronary angiography (CTCA) provides an accurate noninvasive alternative to the invasive assessment of coronary artery disease. However, a specific limitation of CTCA is inability to assess hemodynamic data. OBJECTIVE: We hypothesized that CTCA-derived measurements of contrast within the superior vena cava (SVC) and inferior vena cava (IVC) would correlate to echocardiographic estimations of right atrial and right ventricular pressures. METHODS: Medical records of all patients who underwent both echocardiography and CTCA in our center were reviewed (n = 32). Standard CTCA was performed with a 64-detector CT using test-bolus method for image acquisition timing and iso-osmolar contrast injection through upper extremity vein. The length of the column of contrast reflux into the inferior vena cava (IVC) was correlated to echocardiographically determine tricuspid regurgitation jet velocity (TRV). SVC area change with contrast injection at the level of the bifurcation of the pulmonary artery was also correlated with IVC sniff response by echocardiogram. RESULTS: The reflux column length was interpretable in 27 of 32 patients with a mean length of 10.1 ± 1.1 mm, and a significant bivariate correlation was observed between reflux column length and the tricuspid regurgitant jet velocity (r = 0.84; P \u3c .0001). Mean SVC distensibility ratio was 0.63 ± 0.03; mean IVC sniff response ratio was 0.53 ± 0.03. SVC distensibility correlated to IVC sniff response with a Pearson r of 0.57 (P = .04). CONCLUSION: Quantification of IVC and SVC contrast characteristics during CTCA provides a feasible and potentially accurate method of estimating right atrial and ventricular pressure

Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability

Endothelial to mesenchymal transition (EndMT) plays a major role during development, and also contributes to several adult cardiovascular diseases. Importantly, mesenchymal cells including fibroblasts are prominent in atherosclerosis, with key functions including regulation of: inflammation, matrix and collagen production, and plaque structural integrity. However, little is known about the origins of atherosclerosis-associated fibroblasts. Here we show using endothelial-specific lineage-tracking that EndMT-derived fibroblast-like cells are common in atherosclerotic lesions, with EndMT-derived cells expressing a range of fibroblast-specific markers. In vitro modelling confirms that EndMT is driven by TGF-beta signalling, oxidative stress and hypoxia; all hallmarks of atherosclerosis. `Transitioning' cells are readily detected in human plaques co-expressing endothelial and fibroblast/mesenchymal proteins, indicative of EndMT. The extent of EndMT correlates with an unstable plaque phenotype, which appears driven by altered collagen-MMP production in EndMT-derived cells. We conclude that EndMT contributes to atherosclerotic patho-biology and is associated with complex plaques that may be related to clinical events.J.C.K. and this project were directly supported by National Institutes of Health (NIH) Grant K08HL111330. J.C.K. also acknowledges support from NIH R01HL130423, Fondation Leducq (Transatlantic Network of Excellence Award) and receives research support from AstraZeneca. K.C.M. and V.d'E. are supported by NIH T32HL007824. L.H. is supported by NIH K01HL103176. G.P. is supported by NIH R01GM114434, P30ES023515, U01HL107388, U2CES026561, U2CES026555 and an IBM faculty award. R.H. is supported by NIH R01HL117505, HL119046, HL129814, 128072, P50HL112324 and the Fondation Leducq (Transatlantic Network of Excellence Award). We acknowledge the assistance and technical expertise of the Microscopy, Genomics and Multiscale Biology, and Flow Cytometry Core Facilities and the Center for Comparative Medicine and Surgery of the Icahn School of Medicine at Mount Sinai.S

CD90 Identifies Adventitial Mesenchymal Progenitor Cells in Adult Human Medium- and Large-Sized Arteries

Summary: Mesenchymal stem cells (MSCs) reportedly exist in a vascular niche occupying the outer adventitial layer. However, these cells have not been well characterized in vivo in medium- and large-sized arteries in humans, and their potential pathological role is unknown. To address this, healthy and diseased arterial tissues were obtained as surplus surgical specimens and freshly processed. We identified that CD90 marks a rare adventitial population that co-expresses MSC markers including PDGFRα, CD44, CD73, and CD105. However, unlike CD90, these additional markers were widely expressed by other cells. Human adventitial CD90+ cells fulfilled standard MSC criteria, including plastic adherence, spindle morphology, passage ability, colony formation, and differentiation into adipocytes, osteoblasts, and chondrocytes. Phenotypic and transcriptomic profiling, as well as adoptive transfer experiments, revealed a potential role in vascular disease pathogenesis, with the transcriptomic disease signature of these cells being represented in an aortic regulatory gene network that is operative in atherosclerosis. : MSCs reportedly exist in a specific vascular niche, but these cells have not been well characterized in medium- and large-sized human arteries. To address this, surplus arterial tissues were obtained at surgery and freshly processed. We show that CD90 marks a human adventitial MSC population, with the CD90+ MSC transcriptomic signature being represented in an atherosclerotic regulatory gene network. Keywords: mesenchymal stem cell, adventitia, atherosclersis, cardiovascula

A library of induced pluripotent stem cells from clinically well-characterized, diverse healthy human individuals

A library of well-characterized human induced pluripotent stem cell (hiPSC) lines from clinically healthy human subjects could serve as a useful resource of normal controls for in vitro human development, disease modeling, genotype-phenotype association studies, and drug response evaluation. We report generation and extensive characterization of a gender-balanced, racially/ethnically diverse library of hiPSC lines from 40 clinically healthy human individuals who range in age from 22 to 61 years. The hiPSCs match the karyotype and short tandem repeat identities of their parental fibroblasts, and have a transcription profile characteristic of pluripotent stem cells. We provide whole-genome sequencing data for one hiPSC clone from each individual, genomic ancestry determination, and analysis of mendelian disease genes and risks. We document similar transcriptomic profiles, single-cell RNA-sequencing-derived cell clusters, and physiology of cardiomyocytes differentiated from multiple independent hiPSC lines. This extensive characterization makes this hiPSC library a valuable resource for many studies on human biology. •A library of induced pluripotent stem cells from 40 healthy human subjects•Racially/ethnically diverse subjects of clinically well-characterized health•Whole-genome sequencing identifies variants of mild common phenotypes or incomplete penetrance•Similar physiology of cardiomyocytes from independent hiPSC clones and individuals In this resource, Schaniel et al. report the generation and characterization of a gender-balanced, racially/ethnically diverse library of hiPSC lines from 40 clinically well-characterized healthy human individuals. The authors provide whole-genome sequencing data, ancestry determination, and analysis of mendelian disease genes and risks. Furthermore, similar physiology of cardiomyocytes differentiated from independent hiPSC clones derived from two individuals is documented

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015–2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios