Arteriogenesis versus angiogenesis: similarities and differences

Cardiovascular diseases account for more than half of total mortality before the age of 75 in industrialized countries. To develop therapies promoting the compensatory growth of blood vessels could be superior to palliative surgical surgical interventions. Therefore, much effort has been put into investigating underlying mechanisms. Depending on the initial trigger, growth of blood vessels in adult organisms proceeds via two major processes, angiogenesis and arteriogenesis. While angiogenesis is induced by hypoxia and results in new capillaries, arteriogenesis is induced by physical forces, most importantly fluid shear stress. Consequently, chronically elevated fluid shear stress was found to be the strongest trigger under experimental conditions. Arteriogenesis describes the remodelling of pre-existing arterio-arteriolar anastomoses to completely developed and functional arteries. In both growth processes, enlargement of vascular wall structures was proposed to be covered by proliferation of existing wall cells. Recently, increasing evidence emerges, implicating a pivotal role for circulating cells, above all blood monocytes, in vascular growth processes. Since it has been shown that monocytes/macrophage release a cocktail of chemokines, growth factors and proteases involved in vascular growth, their contribution seems to be of a paracrine fashion. A similar role is currently discussed for various populations of bone-marrow derived stem cells and endothelial progenitors. In contrast, the initial hypothesis that these cells -after undergoing a (trans-)differentiation- contribute by a structural integration into the growing vessel wall, is increasingly challenged

Renditen im Umlageverfahren: Anmerkungen zu einem 'einfachen Zusammenhang'

In der August-Ausgabe 1998 des WIRTSCHAFTSDIENST veröffentlichten wir einen Aufsatz von Dr. Hans H. Glismann und Ernst-Jürgen Hornf mit dem Titel „Renditen in der deutschen gesetzlichen Alterssicherung". Hierzu eine Replik von Stefan Eitenmüller und Winfried Hain sowie anschließend eine Erwiderung von Dr. Hans H. Glismann. --

Langzeitergebnisse der arthroskopischen Meniskusrefixation und der partiellen Meniskektomie unter der speziellen Betrachtung der frühzeitigen Arthroseentwicklung im Kniegelenk

Degenerative Veränderungen im Röntgenbild nach totaler Meniskektomie sind zahlreich beschrieben worden [19;26;39;89;106]. Aber auch nach der partiellen Meniskektomie wird über eine progressive Arthroseentwicklung berichtet [13;27;39;86]. In der vorliegenden retrospektiven Studie werden die Langzeitergebnisse der arthroskopischen Meniskusrefixation im Kniegelenk unter spezieller Betrachtung der frühzeitigen Arthroseentwicklung den Ergebnissen nach partieller Meniskusresektion gegenübergestellt. Im Zeitraum von 1984-96 wurden 81 Patienten arthroskopisch am Innenmeniskus (IM) operiert. 42 Patienten erhielten eine Naht in Inside-out Technik, bei 39 Patienten, mit gleichen präoperativen Kriterien (Alter, Nachbeobachtungszeitraum, Arthrosegrad) wurde der IM partiell reserziert. Der durchschnittliche Nachbeobachtungszeitraum (NUZ) betrug 6,5 Jahre. 35 Patienten wurden mittelfristig in 3,4 J. (NUZ 2-5J.) und 46 Patienten längerfristig in 8,8 J. (NUZ >5J.) nachuntersucht. Aufgrund des zu erwartenden höheren präoperativen Arthrosegrades bei Pat. über 30J., wurden diese getrennt beurteilt. Alle Kniegelenke waren klinisch stabil. Die Evaluation erfolgte mit dem Lysholm, dem Tegner und dem Fairbank Score (Fb). Die Analyse nach Fairbank zeigte, daß bei mittelfristigem NUZ bei allen Patienten nur geringe radiologische Veränderungen auftreten. Längerfristig sind arthrotische Erscheinungen im KG nach partieller Resektion eindeutig häufiger: 50% der Patienten =30 J.) zeigen eine Verschlechterung im Fb Score. Nach IM-Refixation traten degenerative Veränderungen bei 13% der Patienten =30 J.) auf. Ihr ursprüngliches Tegneraktivitätsniveau erlangten im Langzeitverlauf 96,2% der Patienten der Refixationsgruppe und 50% der Patienten der Resektionsgruppe wieder. Im Lysholm Score erzielten die Patienten der Refixationsgruppe 91,5 Punkte, die Patienten der Resektionsgruppe 88,4 Punkte im NUZ. Die Ergebnisse zeigen, daß nach Meniskusrefixation bei geeigneter Rupturform im Langzeitverlauf deutlich geringere degenerative Veränderungen auftreten und sie somit der partiellen Resektion überlegen ist und trotz aufwendigerer Operation und Rehabilitation die Methode der Wahl sein sollte

Mechanical properties and in vitro degradation behavior of additively manufactured phosphate glass particles/fibers reinforced polylactide

Phosphate glass/polylactide (PG/PLA) composites were additively manufactured via fused deposition modeling. The incorporation of 10 wt % PG particles improved the flexural modulus of composites by ~14% (3.53 GPa) but led to 5% reduction in flexural strength (92.4 MPa). The trend was more pronounced as the particle loading doubled. Comparing to a particulate composite of the same weight fraction, milled PG fibers (PGFs) reinforcement led to more effectively improved flexural modulus (~30%, 4.10 GPa). After 28 days of in vitro degradation in phosphate buffered saline, the particulate composites lost more than 30% of their initial mechanical properties, in contrast to less than 10% reduction of strength/modulus reported from fiber reinforced composites. The additively manufactured PG/PLA matrix composites have potential for application as customized bone fixation plates to repair the fractures under modest load‐bearing applications. © 2019 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48171

Activation of the integrins α5β1 and αvβ3 and focal adhesion kinase (FAK) during arteriogenesis

Migration and proliferation of smooth muscle cells (SMC) are important events during arteriogenesis, but the underlying mechanism is still only partially understood. The present study investigates the expression of integrins α5β1 and vβ3 as well as focal adhesion kinase (FAK) and phosphorylated FAK (pY397), key mediators for cell migration and proliferation, in collateral vessels (CV) in rabbit hind limbs induced by femoral ligation or an arteriovenous (AV) shunt created between the distal femoral artery stump and the accompanying femoral vein by confocal immunofluorescence. In addition, the effect of the extracellular matrix components fibronectin (FN), laminin (LN), and Matrigel on expression of these focal adhesion molecules proliferation was studied in cultured SMCs. We found that: (1) in normal vessels (NV), both integrins α5β1 and αvβ3 were mainly expressed in endothelial cells, very weak in smooth muscle cells (SMC); (2) in CVs, both α5β1 and αvβ3 were significantly upregulated (P < 0.05); this was more evident in the shunt-side CVs, 1.5 and 1.3 times higher than that in the ligation side, respectively; (3) FAK and FAK(py397) were expressed in NVs and CVs in a similar profile as was α5β1 and αvβ3; (4) in vitro SMCs cultured on fibronectin (overexpressed in collaterals) expressed higher levels of FAK, FAK (pY397), α5β1, and αvβ3 than on laminin, whereas SMCs growing inside Matrigel expressed little of these proteins and showed no proliferation. In conclusion, our data demonstrate for the first time that the integrin-FAK signaling axis is activated in collateral vessels and that altered expression of FN and LN may play a crucial role in mediating the integrin-FAK signaling pathway activation. These findings explain a large part of the positive remodeling that collateral vessels undergo under the influence of high fluid shear stress

Rentabilitätsvergleiche im Umlage- und Kapitaldeckungsverfahren : Konzepte, empirische Ergebnisse, sozialpolitische Konsequenzen

Die demographischen Veränderungen sind Auslöser einer grundsätzlicheren Debatte über Alterssicherungsverfahren, nämlich der Wahl eines effizienten Finanzierungsverfahrens der Altersvorsorge. Im Zentrum der Debatte steht immer wieder der Renditevergleich zwischen dem Umlage- und dem Kapitaldeckungsverfahren. Ihm gilt dieses Papier. Er ist keineswegs so einfach, wie es oft suggeriert wird, da Versicherungs- und Risikoaspekte, vor allem aber das Übergangsproblem berücksichtigt werden müssen. Der vorliegende Beitrag stellt den wirtschaftstheoretischen Hintergrund mit den wichtigsten relevanten Konzepten dar und präsentiert empirische Schätzungen zur heutigen und Simulationsergebnisse zur zukünftigen Entwicklung der relevanten Renditen. Wir schließen mit den sozialpolitischen Konsequenzen für eine reformierte Altersvorsorge

Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

Articles in International JournalsArteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Deltalike 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic lossand gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/− mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/− mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality

The proteoglycan osteoglycin/mimecan is correlated with arteriogenesis

Arteriogenesis or collateral growth is able to compensate for the stenosis of major arteries. Using differential display RT-PCR on growing and quiescent collateral arteries in a rabbit femoral artery ligation model, we cloned the rabbit full-length cDNA of osteoglycin/mimecan. Osteoglycin was present in the adventitia of collateral arteries as a glycosylated protein without keratan sulfate side chains, mainly produced by smooth muscle cells (SMCs) and perivascular fibroblasts. Northern blot, Western blot, and immunohistochemistry confirmed a collateral artery-specific downregulation of osteoglycin from 6 h to 3 weeks after the onset of arteriogenesis. Treatment of primary SMCs with the arteriogenic protein fibroblast growth factor-2 (FGF-2) resulted in a similar reduction of osteoglycin expression as observed in vivo. Application of the FGF-2 inhibitor polyanethole sulfonic acid (PAS) blocked the downregulation of osteoglycin and interfered with arteriogenesis. From our study we conclude that downregulation of osteoglycin is a fundamental requirement for proper arteriogenesis

Leave Me Alone With Your Symptoms! Social Exclusion at the Workplace Mediates the Relationship of Employee's Mental Illness and Sick Leave

Although a substantial part of employees suffers from a mental illness, the work situation of this population still is understudied. Previous research suggests that people with a mental illness experience discrimination in the workplace, which is known to have detrimental effects on health. Building on the stereotype content model and allostatic load theory, the present study investigated whether employees with a mental illness become socially excluded at the workplace and therefore show more days of sick leave. Overall, 86 employees diagnosed with a mental disorder were interviewed and completed online-surveys. Path analyses supported the hypotheses, yielding a serial mediation: The interview-rated severity of the mental disorder had an indirect effect on the days of sick leave, mediated by the symptomatic burden and the social exclusion at the workplace. In the light of the costs associated with absenteeism the present paper highlights the harmfulness of discrimination. Organizations and especially supervisors need to be attentive for signs of exclusion within their teams and try to counteract as early as possible