Papers by Wolfgang Schaper
Circulation Research, 2004
Bone marrow-Derived cells have been proposed to form new vessels or at least incorporate into gro... more Bone marrow-Derived cells have been proposed to form new vessels or at least incorporate into growing vessels in adult organisms under certain physiological and pathological conditions. We investigated whether bone marrow-Derived cells incorporate into vessels using mouse models of hindlimb ischemia (arteriogenesis and angiogenesis) and tumor growth. C57BL/6 wild-type mice were lethally irradiated and transplanted with bone marrow cells from littermates expressing enhanced green fluorescent protein (GFP). At least 6 weeks after bone marrow transplantation, the animals underwent unilateral femoral artery occlusions with or without pretreatment with vascular endothelial growth factor or were subcutaneously implanted with methylcholanthrene-induced fibrosarcoma (BFS-1) cells. Seven and 21 days after surgery, proximal hindlimb muscles with growing collateral arteries and ischemic gastrocnemius muscles as well as grown tumors and various organs were excised for histological analysis. We ...
Growth stimulation of peripheral and cerebral collaterals to increase intravascular flow in animal models
Gefasschirurgie, Feb 1, 2009
Circulation Research, 2009
Rationale : We previously discovered the human 10T→C (Trp4Arg) missense mutation in exon 2 of the... more Rationale : We previously discovered the human 10T→C (Trp4Arg) missense mutation in exon 2 of the muscle LIM protein (MLP, CSRP3) gene. Objective : We sought to study the effects of this single-nucleotide polymorphism in the in vivo situation. Methods and Results : We now report the generation and detailed analysis of the corresponding Mlp W4R/+ and Mlp W4R/W4R knock-in animals, which develop an age- and gene dosage–dependent hypertrophic cardiomyopathy and heart failure phenotype, characterized by almost complete loss of contractile reserve under catecholamine induced stress. In addition, evidence for skeletal muscle pathology, which might have implications for human mutation carriers, was observed. Importantly, we found significantly reduced MLP mRNA and MLP protein expression levels in hearts of heterozygous and homozygous W4R-MLP knock-in animals. We also detected a weaker in vitro interaction of telethonin with W4R-MLP than with wild-type MLP. These alterations may contribute t...
Augmentation of collateral vessel growth prevents angiogenesis
Journal of Molecular and Cellular Cardiology, 2001
American Journal of …, 2002
0.1152/ajpheart. 01098.2001.Arteriogenesis has been associated with the presence of monocytes/ma... more 0.1152/ajpheart. 01098.2001.Arteriogenesis has been associated with the presence of monocytes/macrophages within the collateral vessel wall. We tested the hypothesis that arteriogenesis is functionally linked to the concentration of circulating blood monocytes. Monocyte ...
Nitric oxide as a stimulator for the expression of TRPV-4 in collateral vessels during arteriogenesis
Deutsche Gesellschaft für Chirurgie, 2009
Bmx/Etk non-receptor tyrosine protein kinase has been implicated in endothelial cell migration an... more Bmx/Etk non-receptor tyrosine protein kinase has been implicated in endothelial cell migration and tube formation in vitro. However, the role of Bmx in vivo is not known. Bmx is highly induced in the vasculature of ischemic hind limbs. We used both mice with a genetic deletion of Bmx (Bmx-KO mice) and transgenic mice expressing a constitutively active form of Bmx under the endothelial Tie-2 enhancer/promoter (Bmx-SK-Tg mice) to study the role of Bmx in ischemia-mediated arteriogenesis/angiogenesis. In response to ischemia, Bmx-KO mice had markedly reduced, whereas Bmx-SK-Tg mice had enhanced, clinical recovery, limb perfusion, and ischemic reserve capacity when compared with nontransgenic control mice. The functional outcomes in these mice were correlated with ischemia-initiated arteriogenesis, capillary formation, and vessel maturation as well as Bmx-dependent expression/activation of TNF receptor 2-and VEGFR2-mediated (TNFR2/VEGFR2-mediated) angiogenic signaling in both hind limb and bone marrow. More importantly,
Journal of thrombosis and thrombolysis, 1997
Problems associated with reperfusion of ischemic myocardium
Developments in Cardiovascular Medicine, 1990
Cardiovascular Research, Sep 1, 2002
Objective: This study was performed to evaluate the cardioprotective role of acidic fibroblast gr... more Objective: This study was performed to evaluate the cardioprotective role of acidic fibroblast growth factor-1 (FGF-1) in transgenic mice with cardiac-specific overexpression of human FGF-1. Methods: Mice were subjected to coronary artery occlusion for 15-75 min with a continuously recorded 3-lead electrocardiogram (ECG). Infarct size was measured and ERK-1 and -2 activity was assessed by Western blot analysis. Creatine kinase and lactate dehydrogenase activity as marker for cell viability were measured in isolated ventricular myocytes subjected to simulated ischemia. Results: Infarct development was markedly delayed in transgenics with first signs of myocardial infarction visible at 45 min after coronary artery occlusion compared to 15 min in wildtype. Maximal infarct size (60% of risk area) did not differ, but transgenics reached maximal infarction after 75 min compared to 45 min in wildtype animals. ECG revealed delayed Q-wave development and delayed ST-segment elevation in transgenics. Creatine kinase and lactate dehydrogenase release was significantly attenuated from isolated transgenic myocytes at 4 and 8 h after simulated ischemia. The delay in infarct development is partially due to a constitutive higher expression of the extracellular signal-regulated kinases ERK-1 and -2 in the myocardium of transgenics. Additionally, injection of the ERK-1 / 2 inhibitor UO126 decreased the cardioprotective effect of FGF-1. Conclusion: Cardiac specific overexpression of FGF-1 provides cardioprotection at the level of the cardiac myocyte, independent from angiogenesis, and at least partially mediated via activation of the mitogen activated protein kinase (MAP) ERK-1 and -2.
Modulation of collateral artery growth in a porcine hindlimb ligation model using MCP-1
Nederlands Tijdschrift Voor Traumatologie, 2003
For an appropriate extrapolation to patients with peripheral arterial obstructive disease, we tes... more For an appropriate extrapolation to patients with peripheral arterial obstructive disease, we tested the efficacy of monocyte chemoattractant protein 1 (MCP-1) treatment in a porcine hindlimb ligation model. In 40 minipigs, a femoral artery ligation was performed. Control animals were examined immediately after ligation (n = 4) or after 2 wk of intra-arterial infusion of PBS (n = 11). A second group of animals was evaluated after intra-arterial infusion of 2.0 microg/h of MCP-1 for 48 h (followed by 12 days of PBS; n = 13) or 2 wk continuously (n = 12). In the terminal experiment after 2 wk, resting flow to the leg and peripheral arterial pressures were assessed without vasodilatation. Subsequently, vascular conductance was determined by using a pump-driven extracorporal circulation during maximal vasodilatation. The results showed that resting blood flow to the hindlimb was 53% of the normal after 2 wk of infusion of PBS, compared with 81% in both MCP-1 treatment groups (P < 0.05). Collateral conductance was 645 +/- 346 ml x min(-1) x mmHg(-1) after 2 wk of infusion with PBS, compared with 1,070 +/- 530 and 1,158 +/- 535 ml x min(-1) x mmHg(-1) after 48 h and 2 wk treatment with MCP-1, respectively (P < 0.05). Modulation of the process of arteriogenesis is feasible in this large animal model via intra-arterial infusion of the Cys-Cys-chemokine MCP-1.
The Cardiovascular Pharmacology of Lidoflazine, a Long-Acting Coronary Vasodilator
Journal of Pharmacology and Experimental Therapeutics, May 1, 1966
Page 1. Lidoflazine, generic name for serial no. R 7904; 1-[4 ,4-di-(4-fluorophenyl)-butyl]- 4-(2... more Page 1. Lidoflazine, generic name for serial no. R 7904; 1-[4 ,4-di-(4-fluorophenyl)-butyl]- 4-(2 ,6-di-methylanilinocarbonyl)-methyl]-piperazine; CIOHHFINIO = 491.60; mp 158-161#{176}C. Received for publication August 23, 1965. 265 ...
Wachstum von Koronarkollateralen. DNS-Synthese und Mitoserate bei Myokardhypoxie
Two signaling receptors for vascular
Methods for the modulation of neovascularization and/or the growth of collateral arteries and/or other arteries from preexisting arteriolar connections
Journal of Vascular Surgery, 1999
Konstruktion und Eigenschaften neur Me?k?pfe zur elektromagnetischen Registrierung der Blutstr?mung
Pflugers Arch Eur J Physiol, 1965
Time course of mitosis and collateral growth following coronary microembolization in the porcine heart
Cell and Tissue Research, Apr 1, 1997
In ischaemic porcine myocardium, the growth of collateral vessels by angiogenesis is observed in ... more In ischaemic porcine myocardium, the growth of collateral vessels by angiogenesis is observed in clusters in the vicinity of focal necroses. Because mitosis of endothelial cells is a prerequisite for angiogenesis, the purpose of this study has been to evaluate the time course of mitosis as an indicator of vascular growth in a porcine model of coronary microembolization. Ischaemia was induced by injection of 25-microm microspheres in the left circumflex artery, followed by tissue collection from non-ischaemic and ischaemic areas of the same heart after 24, 72 or 168 h microembolization. Tissue was studied by histone H3 in-situ hybridization, PCNA/cyclin immunohistochemistry and electron microscopy. The number of blood vessels in ischaemic myocardium was compared with that in normal control tissue. Capillary growth started as early as 24 h after microembolization, as indicated by increasing numbers of proliferating, histone H3- and PCNA/cyclin-positive cells in the necrotic inflammatory foci of the ischaemic area. At 72 h and 168 h, the number of blood vessels was significantly higher in ischaemic than in normal myocardium, whereas at 168 h, mitosis of cells was, as in normal myocardium, a rare event. Coronary microembolization of porcine myocardium thus leads to an increased cellular proliferation rate between 24 h and less than 7 days after the onset of microembolization, followed by enhanced capillary growth. In-situ hybridization with histone H3 and PCNA/cyclin immunohistochemistry seem to be reliable markers for proliferation and vascular growth in non-cancerogenic tissue.
VEGFR-1-selective VEGF homologue PIGF is arteriogenic evidence for a monocyte-mediated mechanism
Circulation Research, 2003
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Papers by Wolfgang Schaper