The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform

Wolfgang Schaper - One of the best experts on this subject based on the ideXlab platform.

  • Involvement of neuronal NO synthase in Collateral Artery growth
    Indian Journal of Biochemistry & Biophysics, 2011
    Co-Authors: J. I. Pagel, Imo E. Hoefer, Julia Borgolte, Borja Fernández, Wolfgang Schaper, Elisabeth Deindl
    Abstract:

    To evaluate the role of neuronal nitric oxides synthase (nNOS) in Collateral Artery growth (arteriogenesis), we analyzed the expression pattern of nNOS at distinct time points on RNA and protein levels in a rabbit and a murine model of peripheral arteriogenesis. In the rabbit model, Northern blot analyses revealed a significant upregulation of nNOS at 6 h (1.6-fold), 12 h (2.2-fold) and 24 h (2.0-fold) after induction of arteriogenesis via femoral Artery ligation, when compared to the sham operated side. In mice, an upregulation of nNOS was also detected using Northern blot (at 6 h, 12 h) and qRT-PCR (12 h: 2.4-fold). On the protein level, nNOS was found to be upregulated 24 h after femoral Artery ligation. Immunohistochemical staining showed that nNOS was localized in endothelial and smooth muscle cells of Collateral arteries, as well as in skeletal muscle and nerves. In summary, our data provide evidence that nNOS is not constitutively expressed, but is induced during arteriogenesis, playing a role in supplying reactive oxygen species such as H 2O2 and low levels of NO.

  • The proteoglycan osteoglycin/mimecan is correlated with arteriogenesis
    Molecular and Cellular Biochemistry, 2009
    Co-Authors: Andreas Kampmann, Imo E. Hoefer, Borja Fernández, Wolfgang Schaper, Elisabeth Deindl, Inka Eitenmuller, Frederic Pipp, Thomas Kubin, René Zimmermann
    Abstract:

    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.

  • The art of arteriogenesis
    Cell Biochemistry and Biophysics, 2005
    Co-Authors: Elisabeth Deindl, Wolfgang Schaper
    Abstract:

    The identification of Collateral Artery growth (arteriogenesis) as the only mechanism to compensate for the loss of an occluded Artery forced us to define the mechanisms responsible for this type of vessel growth. To achieve this, a variety of coronary as well as peripheral models of arteriogenesis have been developed. Based on these studies it is obvious that arteriogenesis obeys different mechanisms than angiogenesis, the sprouting of capillaries. Upon occlusion of an Artery, the blood flow is redirected into preexisting arteriolar anastomoses that experience increased mechanical forces such as shear stress and circum ferential wall stress. The endothelium of the arteriolar connections is then activated, resulting in an increased release of monocyte-attracting proteins as well as an upregulation of adhesion molecules. Upon adherence and extravasation, monocytes promote arteriogenesis by supplying growth factors and cytokines that bind to receptors that are expressed on vascular cells within a limited time frame. Animal studies evidenced that factors, such as monocyte chemoattractant protein-1, granulocyte-monocyte colony-stimulating factor, or transforming growth factor-β_1, that either attract or prolong the lifetime of monocytes efficiently enhance Collateral Artery growth, an effect that was seen only to a minor degree after application of a single growth factor. Bone marrow-derived stems cells and endothelial progenitor cells do not incorporate in growing arteries but, rather, function as supporting cells. Complete elucidation of the mechanisms of arteriogenesis may lead to efficacious therapies counteracting the devastating consequences of vascular occlusive diseases.

  • Arterial regeneration by Collateral Artery growth (arteriogenesis)
    Drug Discovery Today: Disease Models, 2004
    Co-Authors: Matthias Heil, Shawn Wagner, Wolfgang Schaper
    Abstract:

    After birth, blood vessel growth is limited to two major processes. The growth of new capillaries by sprouting or intussusception (see Glossary) after the emergence of ischemia is called angiogenesis. By contrast, arteriogenesis describes the formation of Collateral arteries from a pre-existing arteriolar network after the occlusion of a major Artery. Physical forces, particularly fluid shear stress, induced by the increased blood velocity owing to low distal pressure, are triggers of arteriogenesis. In vivo models for arteriogenesis have been employed in different species to evaluate the mechanisms and to develop potential therapeutic approaches.

  • influence of mechanical cellular and molecular factors on Collateral Artery growth arteriogenesis
    Circulation Research, 2004
    Co-Authors: Matthias Heil, Wolfgang Schaper
    Abstract:

    Growth of Collateral blood vessels (arteriogenesis) is potentially able to preserve structure and function of limbs and organs after occlusion of a major Artery. The success of the remodeling process depends on the following conditions: (1) existence of an arteriolar network that connects the preocclusive with the postocclusive microcirculation; (2) activation of the arteriolar endothelium by elevated fluid shear stress; (3) invasion (but not incorporation) of bone marrow–derived cells; and (4) proliferation of endothelial and smooth muscle cells. Most organs of most mammals including man can rely on the existence of interconnecting arterioles in most organs and tissues with heart being the exception in rodents and pigs. Arterial occlusion lowers the pressure in the distal vasculature thereby creating a pressure gradient favoring increased flow through preexisting Collaterals. This increases fluid shear stress leading to endothelial activation with cellular edema, upregulation of adhesion molecules, mitogenic-, thrombogenic-, and fibrinolytic factors, leading to monocyte invasion with matrix digestion. Smooth muscle cells migrate and proliferate and the vessel enlarges under the influence of increasing circumferential wall stress. Growth factors involved belong to the FGF family and signaling proceeds via the Ras/Raf- and the Rho cascades. Increases in vascular radius and wall thickness restore fluid shear stress and circumferential wall stress to normal levels and growth stops. Although increases in Collateral vessel size are very substantial their maximal conductance amounts to only 40% of normal. Forced increases in FSS can reach almost 100%. This Review is part of a thematic series on Angiogenesis, which includes the following articles: Endothelial Progenitor Cells: Characterization and Role in Vascular Biology Bone Marrow–Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences Influence of Mechanical, Cellular, and Molecular Factors on Collateral Artery Growth (Arteriogenesis) Innate Immunity and Angiogenesis Syndecans Growth Factors and Blood Vessels: Differentiation and Maturation Ralph Kelly Guest Editor

Jan J Piek - One of the best experts on this subject based on the ideXlab platform.

  • Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function.
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, A. Yaël Nossent, Anja M. Van Der Laan, Maurice W.j. De Ronde, Sara-joan Pinto-sietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p

  • circulating micrornas characterizing patients with insufficient coronary Collateral Artery function
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, Anja M. Van Der Laan, Maurice W.j. De Ronde, Yael A Nossent, Sarajoan Pintosietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p<0.05), miR10b (p<0.05), miR30d (p<0.05) and miR126 (p<0.001) in patients with insufficient Collateral network development. We further demonstrated that each of these miRNAs could serve as circulating biomarkers to discriminate patients with low Collateral capacity (p<0.01 for each miRNA). We also determined significantly greater expression of miR30d (p<0.05) and miR126 (p<0.001) in CTO patients relative to healthy controls. CONCLUSION: The present study identifies differentially expressed miRNAs in patients with high versus low coronary Collateral capacity. We have shown that these miRNAs can function as circulating biomarkers to discriminate between patients with insufficient or sufficient Collateralization. This is the first study to identify miRNAs linked to coronary Collateral vessel function in humans.

  • stimulation of Collateral Artery growth travelling further down the road to clinical application
    Heart, 2008
    Co-Authors: Stephan H Schirmer, Jan J Piek, F C Van Nooijen, N Van Royen
    Abstract:

    Collateral Artery growth is a potent natural defence mechanism to prevent death and myocardial infarction in occlusive Artery disease. Given the high prevalence of arterial obstructive disease, a therapeutic compound stimulating Collateral vessel growth could have a major impact on morbidity and mortality world wide. Although experimental studies on the stimulation of arteriogenesis have been promising, not a single drug has been proved to be applicable in clinical practice, either because of lack of efficacy or because of undesired side effects. This review summarises current knowledge on the mechanisms of Collateral Artery growth and examines problems that arise from the clinical implementation of pro-arteriogenic treatments to date. Future directions in the translation from bench to bedside and potential new approaches to the stimulation of vascular growth are discussed.

  • interferon β signaling is enhanced in patients with insufficient coronary Collateral Artery development and inhibits arteriogenesis in mice
    Circulation Research, 2008
    Co-Authors: Stephan H Schirmer, Jan J Piek, Imo E. Hoefer, Perry D Moerland, Joost O Fledderus, Jan Baan, Jose P S Henriques, Rene J Van Der Schaaf, Anton J G Horrevoets, Niels Van Royen
    Abstract:

    Stimulation of Collateral Artery growth in patients has been hitherto unsuccessful, despite promising experimental approaches. Circulating monocytes are involved in the growth of Collateral arteries, a process also referred to as arteriogenesis. Patients show a large heterogeneity in their natural arteriogenic response on arterial obstruction. We hypothesized that circulating cell transcriptomes would provide mechanistic insights and new therapeutic strategies to stimulate arteriogenesis. Collateral flow index was measured in 45 patients with single-vessel coronary Artery disease, separating Collateral responders (Collateral flow index, >0.21) and nonresponders (Collateral flow index, ≤0.21). Isolated monocytes were stimulated with lipopolysaccharide or taken into macrophage culture for 20 hours to mimic their phenotype during arteriogenesis. Genome-wide mRNA expression analysis revealed 244 differentially expressed genes (adjusted P , P

  • Abnormal monocyte recruitment and Collateral Artery formation in monocyte chemoattractant protein-1 deficient mice
    Vascular Medicine, 2004
    Co-Authors: Michiel Voskuil, Imo E. Hoefer, Ivo R. Buschmann, Niels Van Royen, Stijn De Graaf, Christoph Bode, Jan J Piek
    Abstract:

    Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of Collateral Artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of Collateral Artery growth. In a total of 21 MCP-1 -/- as well as 13 of the appropriate genetic background controls ({129Sv/J X C57BI/6J}F1), a femoral Artery ligation was performed. Subsequently, a polyethylene catheter, connected to an osmotic minipump, was inserted retrogradely into the occluded femoral Artery with the tip pointing upstream. Using this technique, PBS (MCP-1 -/-: n = 13 and C57B1/6,1: n = 13) or MCP-1 (JE; MCP-1 -/-: n = 8) was delivered intra-arterially. Seven days after ligation, determination of hind limb flow was assessed by controlled tissue perfusion using differently labeled fluorescent microspheres. MCP-1 -/- mice exhibited a reduction of hind limb flow of 32.9 +/- 9.2% of the unligated hind limb, compared with 55.4 +/- 6.8% in C57B1/6J mice (p

Imo E. Hoefer - One of the best experts on this subject based on the ideXlab platform.

  • circulating micrornas characterizing patients with insufficient coronary Collateral Artery function
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, Anja M. Van Der Laan, Maurice W.j. De Ronde, Yael A Nossent, Sarajoan Pintosietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p<0.05), miR10b (p<0.05), miR30d (p<0.05) and miR126 (p<0.001) in patients with insufficient Collateral network development. We further demonstrated that each of these miRNAs could serve as circulating biomarkers to discriminate patients with low Collateral capacity (p<0.01 for each miRNA). We also determined significantly greater expression of miR30d (p<0.05) and miR126 (p<0.001) in CTO patients relative to healthy controls. CONCLUSION: The present study identifies differentially expressed miRNAs in patients with high versus low coronary Collateral capacity. We have shown that these miRNAs can function as circulating biomarkers to discriminate between patients with insufficient or sufficient Collateralization. This is the first study to identify miRNAs linked to coronary Collateral vessel function in humans.

  • Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function.
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, A. Yaël Nossent, Anja M. Van Der Laan, Maurice W.j. De Ronde, Sara-joan Pinto-sietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p

  • quantification of Collateral Artery growth by automated fluorescent microsphere perfusion
    International Journal of Cardiology, 2012
    Co-Authors: Benjamin Meder, Imo E. Hoefer, Caroline E Bergmann, Andreas Keller, Steffen Just, Hugo A Katus, Ivo R. Buschmann
    Abstract:

    Abstract Background Since their introduction, genetically modified mice have become more and more important to examine molecular mechanisms involved in vascular growth. Today the gold standard for measuring vessel conductivity is to directly assess in vivo perfusion. However, this usually becomes more complicated the smaller the animal, especially due to the need for extensive instrumentation and requirement of maximal vasodilation. Methods We developed an automated system that allows pressure-controlled in vivo perfusion of small animals with differently labeled fluorescent microspheres. Results Besides precise operation of the system (mean pressures divergence 0.08%), automation of small animal microsphere perfusion is reliable and highly accurate in mice with and without femoral Artery occlusion. In sham-operated control mice, which did not undergo femoral occlusion, highly reproducible measurements of hind limb perfusion (right vs. left=1.03±0.037) could be assessed. In mice after unilateral femoral Artery occlusion, mean perfusion ratios of the automated method (ratio occluded vs. non-occluded hind limb=0.598±0.046) were comparable to the manual approach (0.561±0.062). However, inter-individual variances were significantly smaller with the automated system. Conclusion We describe here a novel and innovative technical approach for pressure-controlled fluid handling specifically designed for microsphere perfusion measurements in small animals.

  • Shear induced Collateral Artery growth modulated by endoglin but not by ALK1.
    Journal of Cellular and Molecular Medicine, 2012
    Co-Authors: Leonard Seghers, Imo E. Hoefer, Margreet R. De Vries, Evangelia Pardali, Beerend P. Hierck, Peter Ten Dijke, Marie-josé Goumans, Paul H.a. Quax
    Abstract:

    Transforming growth factor-beta (TGF-β) stimulates both ischaemia induced angiogenesis and shear stress induced arteriogenesis by signalling through different receptors. How these receptors are involved in both these processes of blood flow recovery is not entirely clear. In this study the role of TGF-β receptors 1 and endoglin is assessed in neovascularization in mice. Unilateral femoral Artery ligation was performed in mice heterozygous for either endoglin or ALK1 and in littermate controls. Compared with littermate controls, blood flow recovery, monitored by laser Doppler perfusion imaging, was significantly hampered by maximal 40% in endoglin heterozygous mice and by maximal 49% in ALK1 heterozygous mice. Collateral Artery size was significantly reduced in endoglin heterozygous mice compared with controls but not in ALK1 heterozygous mice. Capillary density in ischaemic calf muscles was unaffected, but capillaries from endoglin and ALK1 heterozygous mice were significantly larger when compared with controls. To provide mechanistic evidence for the differential role of endoglin and ALK1 in shear induced or ischaemia induced neovascularization, murine endothelial cells were exposed to shear stress in vitro. This induced increased levels of endoglin mRNA but not ALK1. In this study it is demonstrated that both endoglin and ALK1 facilitate blood flow recovery. Importantly, endoglin contributes to both shear induced Collateral Artery growth and to ischaemia induced angiogenesis, whereas ALK1 is only involved in ischaemia induced angiogenesis.

  • Involvement of neuronal NO synthase in Collateral Artery growth
    Indian Journal of Biochemistry & Biophysics, 2011
    Co-Authors: J. I. Pagel, Imo E. Hoefer, Julia Borgolte, Borja Fernández, Wolfgang Schaper, Elisabeth Deindl
    Abstract:

    To evaluate the role of neuronal nitric oxides synthase (nNOS) in Collateral Artery growth (arteriogenesis), we analyzed the expression pattern of nNOS at distinct time points on RNA and protein levels in a rabbit and a murine model of peripheral arteriogenesis. In the rabbit model, Northern blot analyses revealed a significant upregulation of nNOS at 6 h (1.6-fold), 12 h (2.2-fold) and 24 h (2.0-fold) after induction of arteriogenesis via femoral Artery ligation, when compared to the sham operated side. In mice, an upregulation of nNOS was also detected using Northern blot (at 6 h, 12 h) and qRT-PCR (12 h: 2.4-fold). On the protein level, nNOS was found to be upregulated 24 h after femoral Artery ligation. Immunohistochemical staining showed that nNOS was localized in endothelial and smooth muscle cells of Collateral arteries, as well as in skeletal muscle and nerves. In summary, our data provide evidence that nNOS is not constitutively expressed, but is induced during arteriogenesis, playing a role in supplying reactive oxygen species such as H 2O2 and low levels of NO.

Niels Van Royen - One of the best experts on this subject based on the ideXlab platform.

  • Circulating MicroRNAs Characterizing Patients with Insufficient Coronary Collateral Artery Function.
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, A. Yaël Nossent, Anja M. Van Der Laan, Maurice W.j. De Ronde, Sara-joan Pinto-sietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p

  • circulating micrornas characterizing patients with insufficient coronary Collateral Artery function
    PLOS ONE, 2015
    Co-Authors: Nazanin Hakimzadeh, Imo E. Hoefer, Stephan H Schirmer, Niels Van Royen, Paul H.a. Quax, Anja M. Van Der Laan, Maurice W.j. De Ronde, Yael A Nossent, Sarajoan Pintosietsma, Jan J Piek
    Abstract:

    BACKGROUND: Coronary Collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of Collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed Collateral arteries. METHODS AND RESULTS: Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary Collateralization were dichotomized based on their Collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI 0.39) Collateral Artery capacity. We confirmed significantly elevated levels of miR423-5p (p<0.05), miR10b (p<0.05), miR30d (p<0.05) and miR126 (p<0.001) in patients with insufficient Collateral network development. We further demonstrated that each of these miRNAs could serve as circulating biomarkers to discriminate patients with low Collateral capacity (p<0.01 for each miRNA). We also determined significantly greater expression of miR30d (p<0.05) and miR126 (p<0.001) in CTO patients relative to healthy controls. CONCLUSION: The present study identifies differentially expressed miRNAs in patients with high versus low coronary Collateral capacity. We have shown that these miRNAs can function as circulating biomarkers to discriminate between patients with insufficient or sufficient Collateralization. This is the first study to identify miRNAs linked to coronary Collateral vessel function in humans.

  • Endothelial glycocalyx dimensions are reduced in growing Collateral arteries and modulate leucocyte adhesion in arteriogenesis
    Journal of Cellular and Molecular Medicine, 2009
    Co-Authors: Sebastian Grundmann, Stephan H Schirmer, Daphne De Groot, Niels Van Royen, Liesbeth H. P. Hekking, Jan A. Post, Mihaela G. Ionita, Bernard M. Van Den Berg, Hans Vink, Martin Moser
    Abstract:

    During Collateral Artery growth, monocytes adhere to the endothelium and secrete cytokines from the perivascular space promoting arteriogenesis. Recently, the endothelial glycocalyx has been shown to modulate leucocyte infiltration in atherogenic regions. The role of this endothelial surface coating in arteriogenesis, however, has not been investigated so far. We now report that local plasma levels of hyaluronic acid are specifically increased in Collateral arterial blood of coronary Artery disease patients and hypothesized that components of the endothelial glycocalyx are shed during arteriogenesis, resulting in decreased glycocalyx dimensions and an increased leucocyte extravasation. In a rabbit model of femoral Artery ligation, electron microscopy revealed a decrease in glycocalyx dimensions in Collateral arteries compared with quiescent anastomoses (67.5 ± 47.2 nm versus 101.0 ± 11.3 nm; P < 0.001). This decrease was correlated with a higher number of perivascular macrophages around Collateral arteries. The additional glycocalyx perturbation by local hyaluronidase infusion almost completely removed the endothelial surface layer and temporarily stimulated leucocyte accumulation in the perivascular space. However, complete perturbation of the glycocalyx by hyaluronidase infusion resulted in a significant attenuation of Collateral Artery growth assessed by microsphere-based perfusion measurements (ml/min/100 mmHg: hyaluronidase: 27.5 ± 3.5; Controls: 47.1 ± 3.83; P < 0.001) and a lower percentage of actively proliferating vascular smooth muscle cells. A decreased expression of the shear-stress regulated pro-arteriogenic genes eNOS and TGF-β1 suggests an impaired mechanotransduction as the underlying mechanisms. For the first time, we describe the role of the endothelial glycocalyx in Collateral Artery growth. Although complete abrogation led to attenuated arteriogenesis, shedding of glycocalyx components is observed during Collateral Artery growth.

  • interferon β signaling is enhanced in patients with insufficient coronary Collateral Artery development and inhibits arteriogenesis in mice
    Circulation Research, 2008
    Co-Authors: Stephan H Schirmer, Jan J Piek, Imo E. Hoefer, Perry D Moerland, Joost O Fledderus, Jan Baan, Jose P S Henriques, Rene J Van Der Schaaf, Anton J G Horrevoets, Niels Van Royen
    Abstract:

    Stimulation of Collateral Artery growth in patients has been hitherto unsuccessful, despite promising experimental approaches. Circulating monocytes are involved in the growth of Collateral arteries, a process also referred to as arteriogenesis. Patients show a large heterogeneity in their natural arteriogenic response on arterial obstruction. We hypothesized that circulating cell transcriptomes would provide mechanistic insights and new therapeutic strategies to stimulate arteriogenesis. Collateral flow index was measured in 45 patients with single-vessel coronary Artery disease, separating Collateral responders (Collateral flow index, >0.21) and nonresponders (Collateral flow index, ≤0.21). Isolated monocytes were stimulated with lipopolysaccharide or taken into macrophage culture for 20 hours to mimic their phenotype during arteriogenesis. Genome-wide mRNA expression analysis revealed 244 differentially expressed genes (adjusted P , P

  • Abnormal monocyte recruitment and Collateral Artery formation in monocyte chemoattractant protein-1 deficient mice
    Vascular Medicine, 2004
    Co-Authors: Michiel Voskuil, Imo E. Hoefer, Ivo R. Buschmann, Niels Van Royen, Stijn De Graaf, Christoph Bode, Jan J Piek
    Abstract:

    Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of Collateral Artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of Collateral Artery growth. In a total of 21 MCP-1 -/- as well as 13 of the appropriate genetic background controls ({129Sv/J X C57BI/6J}F1), a femoral Artery ligation was performed. Subsequently, a polyethylene catheter, connected to an osmotic minipump, was inserted retrogradely into the occluded femoral Artery with the tip pointing upstream. Using this technique, PBS (MCP-1 -/-: n = 13 and C57B1/6,1: n = 13) or MCP-1 (JE; MCP-1 -/-: n = 8) was delivered intra-arterially. Seven days after ligation, determination of hind limb flow was assessed by controlled tissue perfusion using differently labeled fluorescent microspheres. MCP-1 -/- mice exhibited a reduction of hind limb flow of 32.9 +/- 9.2% of the unligated hind limb, compared with 55.4 +/- 6.8% in C57B1/6J mice (p

Ivo R. Buschmann - One of the best experts on this subject based on the ideXlab platform.

  • quantification of Collateral Artery growth by automated fluorescent microsphere perfusion
    International Journal of Cardiology, 2012
    Co-Authors: Benjamin Meder, Imo E. Hoefer, Caroline E Bergmann, Andreas Keller, Steffen Just, Hugo A Katus, Ivo R. Buschmann
    Abstract:

    Abstract Background Since their introduction, genetically modified mice have become more and more important to examine molecular mechanisms involved in vascular growth. Today the gold standard for measuring vessel conductivity is to directly assess in vivo perfusion. However, this usually becomes more complicated the smaller the animal, especially due to the need for extensive instrumentation and requirement of maximal vasodilation. Methods We developed an automated system that allows pressure-controlled in vivo perfusion of small animals with differently labeled fluorescent microspheres. Results Besides precise operation of the system (mean pressures divergence 0.08%), automation of small animal microsphere perfusion is reliable and highly accurate in mice with and without femoral Artery occlusion. In sham-operated control mice, which did not undergo femoral occlusion, highly reproducible measurements of hind limb perfusion (right vs. left=1.03±0.037) could be assessed. In mice after unilateral femoral Artery occlusion, mean perfusion ratios of the automated method (ratio occluded vs. non-occluded hind limb=0.598±0.046) were comparable to the manual approach (0.561±0.062). However, inter-individual variances were significantly smaller with the automated system. Conclusion We describe here a novel and innovative technical approach for pressure-controlled fluid handling specifically designed for microsphere perfusion measurements in small animals.

  • Abnormal monocyte recruitment and Collateral Artery formation in monocyte chemoattractant protein-1 deficient mice
    Vascular Medicine, 2004
    Co-Authors: Michiel Voskuil, Imo E. Hoefer, Ivo R. Buschmann, Niels Van Royen, Stijn De Graaf, Christoph Bode, Jan J Piek
    Abstract:

    Monocyte chemoattractant protein 1 (MCP-1) has been shown to be effective for the stimulation of Collateral Artery formation in small and large animal models. The availability of a genetic knockout mouse enables evaluation of the importance of the role of MCP-1 in the natural course of Collateral Artery growth. In a total of 21 MCP-1 -/- as well as 13 of the appropriate genetic background controls ({129Sv/J X C57BI/6J}F1), a femoral Artery ligation was performed. Subsequently, a polyethylene catheter, connected to an osmotic minipump, was inserted retrogradely into the occluded femoral Artery with the tip pointing upstream. Using this technique, PBS (MCP-1 -/-: n = 13 and C57B1/6,1: n = 13) or MCP-1 (JE; MCP-1 -/-: n = 8) was delivered intra-arterially. Seven days after ligation, determination of hind limb flow was assessed by controlled tissue perfusion using differently labeled fluorescent microspheres. MCP-1 -/- mice exhibited a reduction of hind limb flow of 32.9 +/- 9.2% of the unligated hind limb, compared with 55.4 +/- 6.8% in C57B1/6J mice (p

  • modulation of Collateral Artery growth in a porcine hindlimb ligation model using mcp 1
    American Journal of Physiology-heart and Circulatory Physiology, 2003
    Co-Authors: Michiel Voskuil, Jan J Piek, Imo E. Hoefer, Niels Van Royen, Christoph Bode, Wolfgang Schaper, Randolph Seidler, Brian Guth, Ivo R. Buschmann
    Abstract:

    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 ligat...

  • local monocyte chemoattractant protein 1 therapy increases Collateral Artery formation in apolipoprotein e deficient mice but induces systemic monocytic cd11b expression neointimal formation and plaque progression
    Circulation Research, 2003
    Co-Authors: N Van Royen, Michiel Voskuil, Imo E. Hoefer, Ivo R. Buschmann, Sebastian Grundmann, Wolfgang Schaper, M Bottinger, C Bode, Jan J Piek
    Abstract:

    Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a Collateral circulation on arterial occlusion. The present study served to determine whether these proarteriogenic properties of MCP-1 are preserved in hyperlipidemic apolipoprotein E–deficient (apoE −/− ) mice and whether it affects the systemic development of atherosclerosis. A total of 78 apoE −/− mice were treated with local infusion of low-dose MCP-1 (1 μg/kg per week), high-dose MCP-1 (10 μg/kg per week), or PBS as a control after unilateral ligation of the femoral Artery. Collateral hindlimb flow, measured with fluorescent microspheres, significantly increased on a 1-week high-dose MCP-1 treatment (PBS 22.6±7.2%, MCP-1 31.3±10.3%; P P P P P −/− mice up to 2 months after the treatment. However, the local treatment did not preclude systemic effects on atherogenesis, leading to increased atherosclerotic plaque formation and changes in cellular content of plaques.

  • Direct evidence for tumor necrosis factor-alpha signaling in arteriogenesis.
    Circulation, 2002
    Co-Authors: Imo E. Hoefer, Niels Van Royen, John E Rectenwald, Elizabeth J Bray, Zaher Abouhamze, Michiel Voskuil, Jan J Piek, Ivo R. Buschmann, Lyle L Moldawer, C. Keith Ozaki
    Abstract:

    BACKGROUND: Arteriogenesis serves as an efficient mechanism for flow restoration after arterial occlusion. This process is associated with inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), although their role in arteriogenesis remains unclear. We hypothesized that arteriogenesis is reduced in mice lacking functional TNF-alpha or p55 receptor. To test this hypothesis, we developed a novel microsphere-based murine model of hindlimb perfusion measurement. METHODS AND RESULTS: Unilateral femoral arteries of nude (n=9), TNF-alpha(-/-) (n=9), TNF-alpha receptor p55(-/-) (n=8), and p75(-/-) (n=8) mice as well as their appropriate genetic background controls were occluded. The nude mice underwent laser Doppler hindlimb flux measurements preoperatively, postoperatively, and after 7 days. Seven days after ligation, all animals underwent tissue perfusion determinations using fluorescent microspheres. Laser Doppler findings confirmed acute decrease in flux with falsely normal values after 1 week. Microsphere results from control mice showed perfusion restoration to values approximately 50% of normal within 7 days. TNF-alpha(-/-) mice demonstrated a significant reduction (45.1%) in Collateral Artery perfusion compared with controls (TNF-alpha(-/-) 22.4+/-5.1% versus B6x129 49.7+/-9.3%; P