Jutta Schaper

Max Planck Institute for Heart and Lung Research, Stadt Bad Nauheim, Hesse, Germany

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Publications (296)1228.34 Total impact

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    ABSTRACT: We previously reported excessive growth of collateral vessels in the dog heart during arteriogenesis induced by implantation of an ameroid constrictor around the circumflex branch of the left coronary artery. In the present study, using histology and immunocofocal microscopy, we further investigated how these aberrant collateral vessels form. By comparison with mature collateral vessels the following findings were made: perivascular space was very narrow where damage of the perivascular myocardium occurred; the neointima was very thick, resulting in a very small lumen; elastica van Gieson staining revealed the absence of the internal elastic lamina and of elastic fibers in the adventitia, but abundant collagen in the adventitia as well as in the neointima; smooth muscle cells of the neointima expressed less α-SM actin and little desmin; expression of the fibroblast growth factors aFGF, bFGF and platelet-derived growth factor (PDGF)-AB was observed mainly in the endothelial cells and abluminal region, but transforming growth factor-β1 was only present in the adventitia and damaged myocardium; angiogenesis in the neointima was observed in some collateral vessels expressing high levels of eNOS, and cell proliferation was mainly present in the abluminal region, but apoptosis was in the deep neointima. In conclusion, these data for the first time reveal that the formation of the aberrant collateral vessels in the dog heart involves active extracellular proteolysis and a special expression profile of growth factors, eNOS, cell proliferation and apoptosis. The finding of a narrow perivascular space and perivascular myocardial damage suggests that anatomical constraint is most likely the cause for exacerbated inward remodeling in aberrant collateral vessels in dog heart.
    Full-text · Article · Jan 2016 · Cells Tissues Organs
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    ABSTRACT: Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.
    Full-text · Article · Jul 2015 · PLoS ONE
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    Dataset: 006
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    Dataset: 009
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    Dataset: 007
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    Dataset: 004
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    Dataset: 005
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    Dataset: 008
    H. H. Klein · S. Puschmann · J. Schaper · W. Schaper

    Full-text · Dataset · Jan 2015
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    ABSTRACT: The aim of this study was to characterize the vascular remodeling in the external iliac artery (EIA) and the lower leg muscles in a rabbit shunt model created between the distal stump of the occluded femoral artery and the accompanying vein. Histology and immunoconfocal microscopy were used in this study. We found that: 1) both endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (P-eNOS) proteins were significantly increased in the shunt-side EIA; 2) matrix metalloproteinase-2 (MMP-2) expression was 5.5 times in shunt side EIA over that in normal EIA; 3) intercellular adhension molecule-1 (ICAM-1) expression was strongly induced in endothelial cells (EC) and vascular adhension molecule-1 (VCAM-1) expression was significantly increased in both EC and the adventitia of the shunt-side EIA; 4) augmentation of cell proliferation and extracellular proteolysis by macrophage infiltration was observed in shunt-side EIA; 5) cell proliferation was active in shunt side EIA, but quiet in shunt side lower leg’s arterial vessels; 6) capillary density in shunt side lower leg muscles was 2 times over that in normal side. In conclusion, our data demonstrate the paradigm that the power of shear stress takes the reins in arteriogenesis, whereas ischemia in angiogenesis, but not in arteriogenesis.
    Preview · Article · Feb 2013 · Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry
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    ABSTRACT: Previous studies show that actin-binding Rho activating protein (Abra) is expressed in cardiomyocytes and vascular smooth muscle cells. In this study, we investigated the expression profile of Abra in the central nervous system of normal adult rats by confocal immunofluorescence. Results showed that Abra immunostaining was located in neuronal nuclei, cytoplasm and processes in the central nervous system, with the strongest staining in the nuclei; in the cerebral cortex, Abra positive neuronal bodies and processes were distributed in six cortical layers including molecular layer, external granular layer, external pyramidal layer, internal granular layer, internal pyramidal layer and polymorphic layer; in the hippocampus, the cell bodies of Abra positive neurons were distributed evenly in pyramidal layer and granular layer, with positive processes in molecular layer and orien layer; in the cerebellar cortex, Abra staining showed the positive neuronal cell bodies in Purkinje cell layer and granular layer and positive processes in molecular layer; in the spinal cord, Abra-immunopositive products covered the whole gray matter and white matter; co-localization studies showed that Abra was co-stained with F-actin in neuronal cytoplasm and processes, but weakly in the nuclei. In addition, in the hippocampus, Abra was co-stained with F-actin only in neuronal processes, but not in the cell body. This study for the first time presents a comprehensive overview of Abra expression in the central nervous system, providing insights for further investigating the role of Abra in the mature central nervous system.
    No preview · Article · May 2012 · Neural Regeneration Research
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    ABSTRACT: We studied fibrosis, collagen metabolism, MMPs/TIMPs and cytokine expression in various forms of human heart failure (HF) by quantitative immunofluorescent microscopy, Western blot, zymography, RT-PCR and in situ hybridization. In explanted human hearts with HF due to either dilated (DCM, n=6) or ischemic (ICM-BZ-borderzone, ICM-RZ-remote zone, n=7) or inflammatory (myocarditis, MYO, n=6) cardiomyopathy and 8 controls MMP2, 8, 9, 19, and TIMP1, 2, 3, 4 as well as procollagens I and III (PINP, PIIINP), mature collagen III (IIINTP) and the cross-linked collagen I degradation product (ICTP) were measured. In comparison with controls, MMPs and TIMPs were significantly upregulated ranging (from highest to lowest) from ICM-BZ, DCM, ICM-RZ, MYO for all MMPs with the exception of MMP9 (highest in DCM), and for TIMPs from ICM-BZ, ICM-RZ, DCM and MYO. MMP2 and 9 were activated in all groups. The TIMP/MMP ratio was 1.3 for control, 1.9 in ICM-BZ (TIMP>MMP) and lowered to 1.0 in the other groups. Collagen I/collagen III ratio correlated significantly with the decrease in LVEDP. PINP was higher than ICTP in all groups. PIIINP elevation was present in DCM and ICM-RZ and IIINTP was up to 4-fold augmented in all groups. Fibrosin mRNA was upregulated in ICM-BZ, activin A in MYO but FGF1 and FGF2 remained unchanged. ANP mRNA was increased in all groups. Although different degrees of severity of collagen metabolism, MMP/TIMP imbalance and cytokine expression in diverse forms of HF are present, the end product is collagen deposition. These findings suggest multiple mechanisms acting alone or in concert in fibrosis development in HF.
    No preview · Article · Aug 2011 · International journal of cardiology
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    ABSTRACT: Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.
    Full-text · Article · May 2011 · Circulation Heart Failure
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    ABSTRACT: Innervation plays an important role in development and remodeling of blood vessels. However, very little is known whether innervation is involved in arteriogenesis. In the present study, we tested the hypothesis that innervation may contribute to the process of arteriogenesis induced by ligature of femoral artery in rat/rabbit hind limb with or without denervation. We found that: (1) angiography showed more collateral vessels in the ligature side than that in ligature plus denervation side; (2) collateral vessels in denervation side was characterized by an inward remodeling; (3) in both collateral vessels (CVs) from only femoral ligature side as well as the ligature plus denervation side, ICAM-1 and VCAM-1 expression was up-regulated but increased VCAM-1 was more evident in the adventitia of collateral vessels of only femoral ligature side; (4) 7 days after surgery, in CVs from the femoral ligature side only, numerous macrophages (RAM11 positive cells) and high cell proliferation ratio (ki67 positive cells) were detected, but they were less in the denervation side. In conclusion, our data demonstrate for the first time that neural regulation is one of the factors that contributes to collateral vessel growth in rat/rabbit hind limb ischemic model by showing collateral vessel growth induced by femoral artery ligature is impaired by denervation.
    No preview · Article · Apr 2011 · Molecular and Cellular Biochemistry
  • Stefan Hein · Sawa Kostin · Jutta Schaper
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    ABSTRACT: In this chapter we describe the structural alterations observed in failing human myocardium. We review the current literature and compare these reports with our own findings. One of the earliest significant structural changes is the occurrence of myocyte hypertrophy and a significant degree of reactive fibrosis, which are the major factors causing diastolic dysfunction. Furthermore, we describe equivalents of systolic dysfunction: the ultrastructural changes indicating myocyte degeneration characterized by the reduction of myofilaments, an increase in cytoplasm, and the occurrence of small mitochondria with less cristae. The cytoskeleton: the microtubuli showed densification and desmin was augmented and irregularly arranged, most probably a mechanism compensatory for reduced cellular stability because of loss of sarcomeres. The remaining sarcomeres showed less elements of the sarcomeric skeleton, i.e., of titin, α-actinin, and myomesin, which contributes to sarcomeric instability. Membrane damage leads to ionic imbalance and is caused by either loss or increase of the membrane proteins dystrophin, the vinculin–talin–­integrin complex, and of spectrin. The gap junctional protein connexin 43 of the intercalated disc is likewise reduced and represents the basis of defects of the excitation–contraction coupling. In the extracellular space, an accumulation of blood borne cells indicates a process of chronic low-grade inflammation, which is injurious to the sarcolemma of the myocyte. These different processes involving the interstitium as well as almost all cellular components of the cardiomyocytes will finally lead to myocyte death, either autophagic or oncotic but less apoptotic. It is postulated that fibrosis and myocyte hypertrophy combined with loss of sarcomeres are the structural equivalent of diastolic dysfunction. Systolic dysfunction occurs at a later stage of ­progression to heart failure and is caused by damage of the various ­components of the myocytes in addition to cellular hypertrophy and ­fibrosis. In conclusion, the development of heart failure is a multifactorial event involving the extracellular matrix and almost all cellular components of the myocytes. Therefore; fibrosis as well as myocyte degeneration and cell death are the structural factors determining cardiac dysfunction.
    No preview · Chapter · Jan 2011
  • Song Wu · Xiaoqiong Wu · Wu Zhu · Wei-Jun Cai · Jutta Schaper · Wolfgang Schaper
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    ABSTRACT: Growth factors are viewed as main arteriogenic stimulators for collateral vessel growth. However, the information about their native expression and distribution in collateral vessels is still limited. This study was designed to profile expression of acidic and basic FGF, platelet-derived growth factor (PDGF-AB) and vascular endothelial growth factor (VEGF-A) and its receptor, fetal liver kinase-1 (Flk-1) during arteriogenesis by confocal immunofluorescence in both dog ameroid constrictor model and rabbit arteriovenous shunt model of arteriogenesis. We found that: (1) in normal arteries (NA) in dog heart, aFGF, bFGF, and PDGF-AB all were mainly expressed in endothelial cells (EC) and media smooth muscle cells (SMC), but the expression of aFGF was very weak, with those of the other two being moderate; (2) in collateral arteries (CAs), aFGF, bFGF, and PDGF-AB all were significantly upregulated (P < 0.05); they were present in all the layers of the vascular wall and were 2.1, 1.7, and 1.9 times higher than that in NA, respectively; and (3) in NA in rabbit hind limb, VEGF-A was absent, Flk-1 was only weakly present in endothelial cells, but in one week CAs VEGF-A and Flk-1 were significantly increased in both shunt and ligation sides; this was more evident in the shunt-side CAs, 2.3, and 2 times higher than that in the ligation side, respectively. In conclusion, our data demonstrate for the first time that growth factors, aFGF, bFGF, and PDGF-AB are significantly upregulated in collateral vessels in dog heart, and enhanced VEGF-A and its receptor, Flk-1, are associated with rapid and lasting increased shear stress. These findings suggest that endogenous production of growth factors could be an important factor promoting collateral vessel growth.
    No preview · Article · Oct 2010 · Molecular and Cellular Biochemistry
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    ABSTRACT: We previously discovered the human 10T-->C (Trp4Arg) missense mutation in exon 2 of the muscle LIM protein (MLP, CSRP3) gene. We sought to study the effects of this single-nucleotide polymorphism in the in vivo situation. 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 to an increased nuclear localization of W4R-MLP, which was observed by immunohistochemistry. Given the well-known high frequency of this mutation in Caucasians of up to 1%, our data suggest that (W4R-MLP) might contribute significantly to human cardiovascular disease.
    Full-text · Article · Mar 2010 · Circulation Research
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    ABSTRACT: 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 to an increased nuclear localization of W4R-MLP, which was observed by immunohistochemistry. CONCLUSIONS: Given the well-known high frequency of this mutation in Caucasians of up to 1%, our data suggest that (W4R-MLP) might contribute significantly to human cardiovascular disease.
    No preview · Article · Jan 2010
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    ABSTRACT: Nonsarcomeric alpha-actinin (ACTN-1)-positive clusters have been detected in human myocardium structurally jeopardized by dilated cardiomyopathy, hypertrophy due to aortic stenosis, or chronic hibernation, but have never been detected in normal tissue. To systematically investigate these clusters, immunohistochemistry, electron microscopy, Northern blot and Western blot were performed in human myocardium, isolated rat cardiomyocytes and rabbit smooth muscle cells. ACTN-1-positive clusters were localized in the perinuclear area of cardiomyocytes surrounded by rough endoplasmic reticulum. Quantification of structures containing ACTN-1 showed that it was present in up to 10% of all myocytes in 60% of aortic stenosis patients with severely reduced ejection fraction and in 70% of patients with dilated cardiomyopathy, exclusively in myocytes from hearts with structural degeneration and reduced function. Ultrastructurally, clusters of medium electron density corresponding to the confocal microscopic accumulations were observed in the same tissue samples. The messenger RNA of ACTN-1 was unchanged compared with controls, but a Western blot revealed that the protein was significantly elevated in failing hearts. Because membranes of the endoplasmic reticulum surround the clusters, it was concluded that in the presence of undisturbed transcription, a post-translational malfunction of ACTN-1 glycosylation might lead to storage of this protein. Autophagic and ischemic cell death were observed, but a possible toxic effect of this storage product was excluded because markers of cell death rarely colocalized with ACTN-1. The occurrence of ACTN-1-positive clusters, however, appears to be a useful marker for structural degeneration in failing myocardium.
    Full-text · Article · Sep 2009 · Experimental and clinical cardiology
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    ABSTRACT: Endothelin-1 (ET-1) is an important contributor to ventricular hypertrophy and failure, which are associated with arrhythmogenesis and sudden death. To elucidate the mechanism(s) underlying the arrhythmogenic effects of ET-1 we tested the hypothesis that long-term (24 hrs) exposure to ET-1 impairs impulse conduction in cultures of neonatal rat ventricular myocytes (NRVM). NRVM were seeded on micro-electrode-arrays (MEAs, Multi Channel Systems, Reutlingen, Germany) and exposed to 50 nM ET-1 for 24 hrs. Hypertrophy was assessed by morphological and molecular methods. Consecutive recordings of paced activation times from the same cultures were conducted at baseline and after 3, 6 and 24 hrs, and activation maps for each time period constructed. Gap junctional Cx43 expression was assessed using Western blot and confocal microscopy of immunofluorescence staining using anti-Cx43 antibodies. ET-1 caused hypertrophy as indicated by a 70% increase in mRNA for atrial natriuretic peptide (P < 0.05), and increased cell areas (P < 0.05) compared to control. ET-1 also caused a time-dependent decrease in conduction velocity that was evident after 3 hrs of exposure to ET-1, and was augmented at 24 hrs, compared to controls (P < 0.01). ET-1 increased total Cx43 protein by approximately 40% (P < 0.05) without affecting non- phosphorylated Cx43 (NP-Cx43) protein expression. Quantitative confocal microscopy showed a approximately 30% decrease in the Cx43 immunofluorescence per field in the ET-1 group (P < 0.05) and a reduced field stain intensity (P < 0.05), compared to controls. ET-1-induced hypertrophy was accompanied by reduction in conduction velocity and gap junctional remodelling. The reduction in conduction velocity may play a role in ET-1 induced susceptibility to arrhythmogenesis.
    Full-text · Article · Mar 2009 · Journal of Cellular and Molecular Medicine
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    ABSTRACT: 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 alpha 5 beta 1 and v beta 3 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 alpha 5 beta 1 and alpha v beta 3 were mainly expressed in endothelial cells, very weak in smooth muscle cells (SMC); (2) in CVs, both alpha 5 beta 1 and alpha v beta 3 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 alpha 5 beta 1 and alpha v beta 3; (4) in vitro SMCs cultured on fibronectin (overexpressed in collaterals) expressed higher levels of FAK, FAK (pY397), alpha 5 beta 1, and alpha v beta 3 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.
    Preview · Article · Nov 2008 · Molecular and Cellular Biochemistry

Publication Stats

12k Citations
1,228.34 Total Impact Points

Institutions

  • 2006-2015
    • Max Planck Institute for Heart and Lung Research
      Stadt Bad Nauheim, Hesse, Germany
  • 2001-2007
    • Carolinas Medical Center University
      Charlotte, North Carolina, United States
    • Hunan University
      Ch’ang-sha-shih, Hunan, China
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
    • Central South University
      Ch’ang-sha-shih, Hunan, China
  • 1978-2005
    • Max Planck Institute for Informatics
      Saarbrücken, Saarland, Germany
  • 2004
    • Max-Delbrück-Centrum für Molekulare Medizin
      • Experimental and Clinical Research Center (ECRC)
      Berlín, Berlin, Germany
  • 1977-2004
    • Kerckhoff Klinik
      Stadt Bad Nauheim, Hesse, Germany
  • 1978-2003
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
  • 2002
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Egis Gyógyszergyár Nyrt.
      Budapeŝto, Budapest, Hungary
  • 1998-2001
    • Max Planck Society
      München, Bavaria, Germany
    • Max-Planck-Institut für Ökonomik
      Jena, Thuringia, Germany
  • 2000
    • Carolinas Pain Institute
      Winston-Salem, North Carolina, United States
  • 1996
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1993
    • Hospital Frankfurt Hoechst
      Frankfurt, Hesse, Germany
  • 1981
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
  • 1973
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 1971-1972
    • Janssen Pharmaceutica
      Beersse, Flanders, Belgium