A.S. Peters

Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis.

BACKGROUND Absent in melanoma (AIM2) was recently identified to act as a cytosolic DNA sensor in innate immunity. Considering the role of chronic inflammation in atherosclerosis, we hypothesized that AIM2 may act as a damage signal that is activated in response to cellular stress likewise in vascular cells of larger arteries. We thus addressed AIM2 expression in healthy arterial wall and in different vascular lesions. In addition, AIM2 expression was characterized in cultured human aortic endothelial cells (HAoECs), smooth muscle cells (HAoSMCs), and T/G-HA-vascular smooth muscle cells (VSMCs) in response to different stimuli. METHODS Carotid and aortic lesions from patients who underwent surgery and normal arterial specimens were analyzed by immunohistochemistry for AIM2 expression. Cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs were stimulated in vitro with proinflammatory cytokines (tumor necrosis factor-α, interferon-γ) or poly(dA:dT) and analyzed for AIM2 transcript and protein expression. RESULTS AIM2 was detected in ECs of the intima and vasa vasorum of normal carotid artery and aorta. Moreover, AIM2 was moderately expressed in VSMCs of normal media and intima layers, as well as in VSMCs of atherosclerotic lesions. Increased AIM2 expression was detected around the necrotic core of atherosclerotic carotid lesions and in the vasa vasorum neovasculature of aortic aneurysms. Subsequent in vitro analysis identified an endogenous AIM2 expression in cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs that was markedly increased upon treatment of the cells with tumor necrosis factor-α, interferon-γ, or cytosolic DNA. CONCLUSIONS ECs and VSMC are able to respond to inflammatory signals by upregulation of AIM2 expression, indicating a role of AIM2 in vascular pathogenesis.

Penetrating aortic ulcer

In addition to classic aortic dissection and intramural hematoma, acute aortic syndrome also includes penetrating aortic ulcers (PAU). The recent advent of highly detailed axial imaging allows closer assessment of PAU and its pathophysiology. However, there is still ongoing discussion about the natural history of the disease, leading to challenging questions concerning the optimal treatment strategy, particularly in asymptomatic patients. In this review, current indications for treatment, with an emphasis on PAU repair in the endovascular era, are discussed.ZusammenfassungDas penetrierende Aortenulkus (PAU) zählt mit dem intramuralen Hämatom und der klassischen Aortendissektion zur Entität des akuten Aortensyndroms. Trotz moderner Schnittbildgebung, welche eine hochauflösende Darstellung dieser Aortenpathologie erlaubt, sind die dem PAU zugrunde liegenden pathophysiologischen Zusammenhänge noch nicht vollständig geklärt. Aufgrund der unzureichenden Datenlage bezüglich des natürlichen Verlaufs der Erkrankung bestehen nach wie vor offene Fragen hinsichtlich der optimalen Behandlungsstrategie. Dies trifft insbesondere bei klinisch asymptomatischen Patienten zu. In der vorliegenden Übersichtsarbeit werden aktuelle Behandlungsindikationen und Therapieansätze bei PAU mit dem Schwerpunkt der endovaskulären Versorgung diskutiert.

Penetrating aortic ulcer: defining risks and therapeutic strategies.

In addition to classic aortic dissection and intramural hematoma, acute aortic syndrome also includes penetrating aortic ulcers (PAU). The recent advent of highly detailed axial imaging allows closer assessment of PAU and its pathophysiology. However, there is still ongoing discussion about the natural history of the disease, leading to challenging questions concerning the optimal treatment strategy, particularly in asymptomatic patients. In this review, current indications for treatment, with an emphasis on PAU repair in the endovascular era, are discussed.ZusammenfassungDas penetrierende Aortenulkus (PAU) zählt mit dem intramuralen Hämatom und der klassischen Aortendissektion zur Entität des akuten Aortensyndroms. Trotz moderner Schnittbildgebung, welche eine hochauflösende Darstellung dieser Aortenpathologie erlaubt, sind die dem PAU zugrunde liegenden pathophysiologischen Zusammenhänge noch nicht vollständig geklärt. Aufgrund der unzureichenden Datenlage bezüglich des natürlichen Verlaufs der Erkrankung bestehen nach wie vor offene Fragen hinsichtlich der optimalen Behandlungsstrategie. Dies trifft insbesondere bei klinisch asymptomatischen Patienten zu. In der vorliegenden Übersichtsarbeit werden aktuelle Behandlungsindikationen und Therapieansätze bei PAU mit dem Schwerpunkt der endovaskulären Versorgung diskutiert.

A Glyoxalase-1 Knockdown Does Not Have Major Short Term Effects on Energy Expenditure and Atherosclerosis in Mice

Objective. Glyoxalase-1 is an enzyme detoxifying methylglyoxal (MG). MG is a potent precursor of advanced glycation endproducts which are regarded to be a key player in micro- and macrovascular damage. Yet, the role of Glo1 in atherosclerosis remains unclear. In this study, the effect of Glo1 on mouse metabolism and atherosclerosis is evaluated. Methods. Glo1 knockdown mice were fed a high fat or a standard diet for 10 weeks. Body weight and composition were investigated by Echo MRI. The PhenoMaster system was used to measure the energy expenditure. To evaluate the impact of Glo1 on atherosclerosis, Glo1KD mice were crossed with ApoE-knockout mice and fed a high fat diet for 14 weeks. Results. Glo1 activity was significantly reduced in heart, liver, and kidney lysates derived from Glo1KD mice. Yet, there was no increase in methylglyoxal-derived AGEs in all organs analyzed. The Glo1 knockdown did not affect body weight or body composition. Metabolic studies via indirect calorimetry did not show significant effects on energy expenditure. Glo1KD mice crossed to ApoE−/− mice did not show enhanced formation of atherosclerosis. Conclusion. A Glo1 knockdown does not have major short term effects on the energy expenditure or the formation of atherosclerotic plaques.

Glyoxalase I (Glo1) and its metabolites in vascular disease

Glo1 (glyxoalase I) is a cytosolic protein expressed in all mammalian cells. Its physiological function is the detoxification of MG (methylglyoxal), which is a potent precursor of AGEs (advanced glycation end-products). Although the impact of AGEs on different forms of vascular diseases has been intensively investigated, the evidence for the involvement of Glo1 and MG is still scarce. Recently, several studies have provided significant evidence for Glo1 having a protective effect on microvascular complications in diabetic patients, such as retinopathy and nephropathy. Regarding macrovascular complications, especially atherosclerotic lesions, the impact of Glo1 is even less clear. In the present article, we review the latest findings regarding the role of Glo1 and MG in vascular biology and the pathophysiology of micro- and macro-vascular disease.

Electron cyclotron resonance ion source experience at the Heidelberg Ion Beam Therapy Center.

Radiotherapy with heavy ions is an upcoming cancer treatment method with to date unparalleled precision. It associates higher control rates particularly for radiation resistant tumor species with reduced adverse effects compared to conventional photon therapy. The accelerator beam lines and structures of the Heidelberg Ion Beam Therapy Center (HIT) have been designed under the leadership of GSI, Darmstadt with contributions of the IAP Frankfurt. Currently, the accelerator is under commissioning, while the injector linac has been completed. When the patient treatment begins in 2008, HIT will be the first medical heavy ion accelerator in Europe. This presentation will provide an overview about the project, with special attention given to the 14.5 GHz electron cyclotron resonance (ECR) ion sources in operation with carbon, hydrogen, helium, and oxygen, and the experience of one year of continuous operation. It also displays examples for beam emittances, measured in the low energy beam transport. In addition to the outlook of further developments at the ECR ion sources for a continuously stable operation, this paper focuses on some of the technical processings of the past year.

Test bench to commission a third ion source beam line and a newly designed extraction system

The HIT (Heidelberg Ion Beam Therapy Center) is the first hospital-based treatment facility in Europe where patients can be irradiated with protons and carbon ions. Since the commissioning starting in 2006 two 14.5 GHz electron cyclotron resonance ion sources are routinely used to produce a variety of ion beams from protons up to oxygen. In the future a helium beam for regular patient treatment is requested, therefore a third ion source (Supernanogan source from PANTECHNIK S.A.) will be integrated. This third ECR source with a newly designed extraction system and a spectrometer line is installed at a test bench at HIT to commission and validate this section. Measurements with different extraction system setups will be presented to show the improvement of beam quality for helium, proton, and carbon beams. An outlook to the possible integration scheme of the new ion source into the production facility will be discussed.

Progress in ion source injector development at the ion beam therapy center (Heidelberg Ion Beam Therapy Center).

Radiotherapy with heavy ions is an upcoming cancer treatment method with to date unachieved precision. It associates higher control rates particularly for radio-resistant tumor species with reduced adverse effects compared to conventional photon therapy. At Heidelberg Ion Beam Therapy Center two 14.5 GHz electron cyclotron resonance ion sources are routinely used to produce a variety of ion beams from protons up to oxygen. The operating time is 330 days per year; our experience after 3 yr of continuous operation will be presented, with special emphasis on stability and breakdowns of components. In addition, the latest enhancement and the results for the operation will be shown.

Xenopericardial self-made tube grafts in infectious vascular reconstructions: Preliminary results of an easy and ready to use surgical approach.

Purpose Infections are a major setback of vascular reconstruction and associated with considerable morbidity and mortality. We evaluated retrospectively our results with self-made bovine pericardial grafts in infected vessel revascularization versus standard graft material. Basic methods Retrospective analysis of 9 patients with bovine reconstruction and 10 patients with miscellaneous grafts (vein, homograft) for vascular infections. Principal findings Infection-free rate of the pericardial group was 100% in 17 months. For patients after reconstructions with miscellaneous grafts, the infection-free rate was 82% in 45 months. Overall in-hospital mortality was 10.5%. There were no in-hospital deaths in the pericardial group. Graft patency of the whole cohort was 100%. The median follow up was 11.74 months. Conclusion Self-made bovine pericardial tube grafts can be crafted to almost any size and adjusted to complex anatomic requirements. The use was feasible in various situations and was associated with good preliminary results concerning patency and reinfection.

Device Conformability and Morphological Assessment After TEVAR for Aortic Type B Dissection: A Single-Centre Experience with a Conformable Thoracic Stent-Graft Design.

Background The aim of this study was to analyze device conformability in TEVAR of acute and chronic (a/c) type B aortic dissections (TBAD) using the Gore Conformable Thoracic Aortic Stent-graft (CTAG). Material/Methods From January 1997 to February 2014, a total of 90 out of 405 patients in our center received TEVAR for TBAD. Since November 2009, 23 patients (16 men; median age: 62 years) were treated with the CTAG. Indications were complicated aTBAD in 15 (65%) and expanding cTBAD in 8 (35%) patients. Primary endpoints were the assessment of device conformability by measuring the distance (D) from the radiopaque gold band marker (GM) at the proximal CTAG end to the inner curvature (IC) of the arch on parasagittal multiplanar reformations of CT angiography, as well as the evaluation of aortic diameter changes following TEVAR. Median follow-up was 13.3 months (range: 2 days to 35 months). Results Primary and secondary success rates were 91.3% (21/23) and 95.6% (22/23), respectively. There was 1 type Ia endoleak, retrograde dissection or primary conversion was not observed. Median GM-IC-D was 0 mm (range: 0 mm to 10 mm). GM-IC-D was associated with zone 2 placement compared to zone 3 (P=0.036). There was no association between GM-IC-D formation and arch type. In aTBAD cases the true lumen significantly increased after TEVAR (P=0.017) and the false lumen underwent shrinkage (P=0.025). In cTBAD patients the false lumen decreased after TEVAR (P=0.036). Conclusions The CTAG shows favorable conformability and wall apposition in challenging arch pathologies such as TBAD.