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Johannes Jeschke

Bio: Johannes Jeschke is an academic researcher from Innsbruck Medical University. The author has contributed to research in topics: Endothelium & Secretoneurin. The author has an hindex of 8, co-authored 9 publications receiving 297 citations.

Papers
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TL;DR: Catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor–dependent mechanism, indicating induction of arteriogenesis and postnatal vasculogenesis.
Abstract: Rationale:The neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Objective:Catestatin shares several functions with angiogenic factors. We therefore reasoned that catestatin induces growth of new blood vessels. Methods and Results:Catestatin induced migration, proliferation, and antiapoptosis in endothelial cells and exerted capillary tube formation in vitro in a Matrigel assay, and such effects were mediated via G protein, mitogen-activated protein kinase, and Akt. Catestatin-induced endothelial cell functions are further mediated by basic fibroblast growth factor, as shown by blockade of effects by a neutralizing fibroblast growth factor antibody. Furthermore, catestatin released basic fibroblast growth factor from endothelial cells and stimulated fibroblast growth factor signaling. In addition to its function on endothelial cells, catestatin also exerted effects on endothelial progenitor cells and vascular smooth muscle cells. In vivo, catestat...

90 citations

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TL;DR: Hypoxia up‐regulates the angiogenic cytokine secretoneurin via an HIF‐1α‐ and basic FGF‐dependent pathway in muscle cells by hypoxia‐inducible factor‐1 α and basic fibroblast growth factor‐dependent mechanisms.
Abstract: Expression of angiogenic cytokines like vascular endothelial growth factor is enhanced by hypoxia. We tested the hypothesis that decreased oxygen levels up-regulate the angiogenic factor secretoneurin. In vivo, muscle cells of mouse ischemic hind limbs showed increased secretoneurin expression, and inhibition of secretoneurin by a neutralizing antibody impaired the angiogenic response in this ischemia model. In a mouse soft tissue model of hypoxia, secretoneurin was increased in subcutaneous muscle fibers. In vitro, secretoneurin mRNA and protein were up-regulated in L6 myoblast cells after exposure to low oxygen levels. The hypoxia-dependent regulation of secretoneurin was tissue specific and was not observed in endothelial cells, vascular smooth muscle cells, or AtT20 pituitary tumor cells. The hypoxia-dependent induction of secretoneurin in L6 myoblasts is regulated by hypoxia-inducible factor-1α, since inhibition of this factor using si-RNA inhibited up-regulation of secretoneurin. Induction of secret...

63 citations

Journal ArticleDOI
TL;DR: The vascularization of the supraclavicular skin depends on skin perforators coming from the transverse cervical artery and draining into the superficial venous plexus and, based on these vessels, a reliable free suprAClavicular flap seems to be safe to harvest, with the donor-site scar lying in the suPRac Lavicular crease.
Abstract: Background:The supraclavicular skin has been studied extensively and used as a pedicled flap for face and neck reconstruction. Its use as a free flap has not paralleled its use as a pedicled flap. The authors performed an anatomical investigation to assess the possibility of harvesting a free suprac

49 citations

Journal ArticleDOI
TL;DR: The data indicate that gene therapy with secretoneurin induces therapeutic angiogenesis, arteriography, and vasculogenesis in the hindlimb ischemia model by a nitric oxide–dependent mechanism.
Abstract: Rationale: The neuropeptide secretoneurin induces angiogenesis and postnatal vasculogenesis and is upregulated by hypoxia in skeletal muscle cells. Objective: We sought to investigate the effects of secretoneurin on therapeutic angiogenesis. Methods and Results: We generated a secretoneurin gene therapy vector. In the mouse hindlimb ischemia model secretoneurin gene therapy by intramuscular plasmid injection significantly increased secretoneurin content of injected muscles, improved functional parameters, reduced tissue necrosis, and restored blood perfusion. Increased muscular density of capillaries and arterioles/arteries demonstrates the capability of secretoneurin gene therapy to induce therapeutic angiogenesis and arteriogenesis. Furthermore, recruitment of endothelial progenitor cells was enhanced by secretoneurin gene therapy consistent with induction of postnatal vasculogenesis. Additionally, secretoneurin was able to activate nitric oxide synthase in endothelial cells and inhibition of nitric oxi...

47 citations

Journal ArticleDOI
TL;DR: Based on the results of this investigation, a free supraclavicular transverse cervical artery perforator (STCAP) flap seems to be feasible pedicled on perforators from the transversal cervical artery and drained by the superficial cervical vein.
Abstract: Vessels in the supraclavicular area and their contribution to skin vascularization have always been studied for flaps planning in head and neck reconstruction and many pedicled flaps have been described based on those vessels. Little has been written instead about the vascularization of the supraclavicular skin itself for the use as a free flap. The purpose of this anatomical study was to assess the vascularization of the supraclavicular skin and the possibility of finding an adequate pedicle to harvest it as a free flap in order to close the donor site directly. A total of 25 cadavers, 10 formalin fixed and 15 fresh, have been studied in cooperation with the Division for Clinical–Functional Anatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria and the Laboratoire d’Anatomie, Universitee R. Descartes, Paris, France. The supraclavicular skin was nourished by perforators coming from the transverse cervical artery and constantly present in an average number of four. Venous drainage was accomplished through the superficial cervical vein, and not through the venae comitantes of the transverse cervical artery. Based on the results of this investigation, a free supraclavicular transverse cervical artery perforator (STCAP) flap seems to be feasible pedicled on perforators from the transverse cervical artery and drained by the superficial cervical vein. Due to its thickness and skin texture, it can be indicated for facial and intraoral defects, with the limitations of a relatively short pedicle. Primary closure of the donor site can be accomplished concealing the scar in the neck crease.

31 citations


Cited by
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TL;DR: The structure and function of granins and granin-derived peptides and expansive new genetic evidence are reviewed, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion.
Abstract: The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers.

289 citations

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TL;DR: Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation and may keep a proportion of MSC in a resting state under physiological conditions.
Abstract: Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

281 citations

Journal ArticleDOI
TL;DR: Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.
Abstract: Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by re-programming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.

257 citations

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TL;DR: Akermanite ceramic, an appropriate Si ion concentration source, could induce angiogenesis through increasing gene expression of proangiogenic cytokine receptors and up-regulated downstream signaling, and is the first Si-containing ceramic demonstrated to be capable of inducingAngiogenesis during bone regeneration.

236 citations

Journal ArticleDOI
TL;DR: In this article, the regenerative capacity of proangiogenic cells (PACs) was investigated in the context of postischemic neovascularization, and it was shown that cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms.
Abstract: Rationale:Circulating proangiogenic cells (PACs) support postischemic neovascularization. Cardiovascular disease and diabetes mellitus impair PAC regenerative capacities via molecular mechanisms th...

176 citations