Citations

Owing to recent progress in analytical techniques, metallomics are evolving from detecting distinct trace metals in a defined state to monitor the dynamic changes in the abundance and location of trace metals in vitro and in vivo. Vascular metallomics is an emerging field that studies the role of trace metals in vasculature. This review will introduce common metallomics techniques including atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, inductively coupled plasma-mass spectrometry and X-ray fluorescence spectrometry with a summary table to compare these techniques. Moreover, we will summarize recent research findings that have applied these techniques to human population studies in cardiovascular diseases, with a particular emphasis on the role of copper in these diseases. In order to address the issue of interdisciplinary studies between metallomics and vascular biology, we will review the progress of efforts to understand the role of copper in neovascularization. This recent advance in the metallomics field may be a powerful tool to elucidate the signaling pathways and specific biological functions of these trace metals. Finally, we summarize the evidence to support the notion that copper is a dynamic signaling molecule. As a future direction, vascular metallomics studies may lead to the identification of targets for diagnosis and therapy in cardiovascular disease.

Object Acute revascularization has been associated with improved stroke outcomes. The Prolyse in Acute Cerebral Thromboembolism (PROACT II) trial achieved recanalization rates of 66%. The Multi Mechanical Embolus Removal in Cerebral Ischemia (Multi MERCI) trial achieved recanalization in 70% of patients. However, these interventional tools are not always successful. The Enterprise vascular reconstruction device was recently introduced for treatment of cerebral aneurysms previously untreatable with endovascular techniques. The authors evaluated a multicenter experience using this stent as a salvage revascularization tool for acute stroke treatment. Methods Four medical centers participated in a retrospective review of endovascularly treated patients with acute stroke for cases treated with the Enterprise stent after routine interventions had been unsuccessful. Data collected included preprocedure information, intraprocedure findings, and outcomes. Results Twenty patients with acute stroke (mean age 61.6 ± 22 years) were treated with the Enterprise stent. Ten patients received intravenous recombinant tissue plasminogen activator before catheter intervention, without improvement. Intraarterial interventions attempted unsuccessfully before Enterprise deployment included the Merci retriever (12 patients), angioplasty (7 patients), glycoprotein IIb–IIIa inhibitor administration (12 patients), intraarterial nitroglycerin (1 patient), Wingspan stent deployment (3 patients), and Xpert stent deployment (1 patient). The mean preintervention National Institutes of Health Stroke Scale (NIHSS) score was 17 ± 6 (median 17). All patients presented with a Thrombolysis in Myocardial Infarction (TIMI) score of 0 or 1. Revascularization was achieved in all patients (75% with a TIMI score of 3, 25% with a TIMI score of 2). Improvement (≥ 4 points on the NIHSS) was documented in 75% of patients. Mean NIHSS improvement from intervention to discharge was 8 ± 7 points (median 9 points). Conclusions These preliminary data suggest a potential benefit to the use of the Enterprise stent when routine intervention methods fail.

Nuclear factor κB (NF-κB) is one of the main transcription factors involved in regulating apoptosis, inflammation, chronic liver disease, and cancer progression. The IKK complex mediates NF-κB activation and deletion of its regulatory subunit NEMO in hepatocytes (NEMOΔhepa) triggers chronic inflammation and spontaneous hepatocellular carcinoma development. We show that NEMOΔhepa mice were resistant to Fas-mediated apoptosis but hypersensitive to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as the result of a strong up-regulation of its receptor DR5 on hepatocytes. Additionally, natural killer (NK) cells, the main source of TRAIL, were activated in NEMOΔhepa livers. Interestingly, depletion of the NK1.1+ cells promoted a significant reduction of liver inflammation and an improvement of liver histology in NEMOΔhepa mice. Furthermore, hepatocyte-specific NEMO deletion strongly sensitized the liver to concanavalin A (ConA)–mediated injury. The critical role of the NK cell/TRAIL axis in NEMOΔhepa livers during ConA hepatitis was further confirmed by selective NK cell depletion and adoptive transfer of TRAIL-deficient−/− mononuclear cells. Our results uncover an essential mechanism of NEMO-mediated protection of the liver by preventing NK cell tissue damage via TRAIL/DR5 signaling. As this mechanism is important in human liver diseases, NEMOΔhepa mice are an interesting tool to give insight into liver pathophysiology and to develop future therapeutic strategies.

The constitutive equation with stress-dependent coefficients for laminated composite is derived and employed for iterative determination of myocardial fiber’s stiffness equation Ef = Kσf + C from myocardial strip’s stiffness equation Es = Ksσs + Cs. The strip’s stiffness constants Ks and Cs are estimated by the least-square curve fitting of the stress-strain data experimentally obtained from uniaxially stretching of strips of left ventricular heart wall excised from seven canine hearts. The values of K and C computed at selected fiber orientations across the thickness of the strip and using three, five, and ten-layer approximations are reported.