Christian Weber

..Vascular pathologies comprise platelet activation and concomitant generation of platelet microparticles (PMPs). We hypothesized that PMPs may interact with EOCs in the context of vascular injury and modulate their regenerative potential...

..The close linkage between platelets and chemokines as culprits in the pathogenesis of vascular diseases may provide a valuable target for selective interventions...

..Improved understanding of the selective contributions of specific cell types to atherogenesis will pave the way for new targeted approaches to therapy...

..This Review summarizes recent progress and future directions in understanding the role of JAMs as 'gate keepers' in inflammation and vascular pathology...

..Macrophage migration inhibitory factor (MIF), a cytokine that controls cell-mediated inflammatory responses, is upregulated in atherogenesis; however, its functional contribution to lesion development has not been evaluated...

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..This model could establish how signals conferred by various chemokines are integrated for the combinatorial control of leukocyte responses...

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..It is unknown whether these functions can be inhibited by soluble forms of JAM-A, whether JAM-A is expressed on atherosclerotic endothelium, and whether it participates in atherogenic recruitment of mononuclear cells...

..This mechanism may explain reduced neointimal macrophage infiltration and lesion formation in CCR2-deficient apoE-/- mice...

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..In conclusion, we have identified a NF-kappaB-mediated proinflammatory phenotype of niSMCs that is characterized by increased P-selectin and chemokine expression and thereby effectively supports leukocyte recruitment...

..Novel stents loaded with an integrin-binding cyclic Arg-Gly-Asp peptide (cRGD) were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting endothelial progenitor cells (EPCs)...

..We studied the role of PMPs in delivering RANTES and promoting monocyte recruitment...

..The aim of this study was to elucidate the role of angio-associated migratory cell protein (AAMP) for the migration of vascular smooth muscle cells (SMCs) and for the development of neointimal hyperplasia after vascular injury...

..In the present study, we examined the contribution of the C5a receptor (C5aR) to neointima formation in apolipoprotein E-deficient mice employing a C5aR antagonist (C5aRA) and a C5aR-blocking monoclonal antibody...

..Here, we examined the contribution of the complement cascade to neointima formation in apolipoprotein E-deficient mice using a C1-esterase inhibitor (C1-inhibitor)...

..2 +/- 3.0 cells/mm(2), macrophages 56.02 +/- 9.93 cells/mm(2), medium 46.35 +/- 9.03 cells/mm(2), P < 0.05) suggests that the underlying mechanism of augmented left ventricular function might be based on inflammatory processes...

..We investigated the influence of the transcriptional regulator Y-box binding protein (YB)-1 on CCL5 expression and wire-induced neointimal hyperplasia...

..In summary, specific MMP-2 blockade prevents sympathetic nerve sprouting (SNS) by inhibition of pro-NGF conversion while losartan abolishes HFES-induced SNS by reducing total NGF, MMP-2 and MT1-MMP expression...

..Although junctional adhesion molecule (JAM)-C has been implicated in the control of inflammatory leukocyte recruitment, its role in neointima formation after arterial injury has not been elucidated...

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..Since human umbilical vein endothelial cells (HUVEC) harbor the potential for transdifferentiation, we studied the functional effects of HUVEC transplantation in a rat model of MI...

..These results imply a combined benefit of EPCs+SDF-1alpha in the treatment of myocardial infarction...

..Nevertheless, the calcineurin-NFAT pathway may provide promising starting points for new pharmacological strategies to prevent SNS in the heart...

..Here, we investigate the effect of hypercholesterolemia on peripheral neutrophil counts, neutrophil recruitment to atherosclerotic lesions, and the importance of neutrophils in atherosclerotic lesion formation in Apoe(-/-) mice...

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..The aim of this study was to analyze the association of polymorphisms of five candidate genes with the outcome of consecutive patients admitted to a medical ICU...

..Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice...

..These results establish the in vivo relevance of chemokine heteromers and show the potential of targeting heteromer formation to achieve therapeutic effects...

..In summary, this study provides evidence that high-rate electrical stimulation of sympathetic neurons mediates nerve sprouting by an increase in NGF expression that targets the TrkA receptor in an autocrine/paracrine manner...

..Thus, the N-like loop in MIF is critical for MIF's noncognate interaction with CXCR2 and proatherogenic functions. The 2-site binding model that explains chemokine receptor activation also applies to MIF...

..048 and p <0.001), respectively, whereas mean intimal hyperplasia thickness treated with dexamethasone-eluting stents was similar to those lesions treated with bare metal stents...

..Understanding the complex molecular interactions of the injured vessel wall with circulating monocytes may enable therapeutic targeting to prevent the development of restenosis...

..Thus, CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling...

..Thus, multiple platelet-derived chemokines and processable precursors, which can be presented by specific endothelial proteoglycans, may contribute and cooperate differentially to induce monocyte recruitment...

..Thus, the statin dose during chronic and continuous treatment independently predicts reduced numbers of circulating as well as isolated EPCs in patients with CAD...

..This may have implications for the modulation of inflammatory recruitment by platelet-derived chemokines...

..In conclusion, our data clearly demonstrate the importance of CXCR2 for the homing of circulating EPCs to sites of arterial injury and for endothelial recovery in vivo...

..We show that YB-1 is a cell-type specific regulator of CCL5 expression in infiltrating T-cells and monocytes/macrophages and acts as an adaptive controller of inflammation during kidney allograft rejection...

..This study highlights functions of microRNAs in health and disease that may extend to the recruitment of progenitor cells during other forms of tissue repair or homeostasis...

..In conclusion, we describe a previously unexplored antifibrotic function of MIF that is mediated by the CD74/AMPK signaling pathway in HSCs. The results imply MIF and CD74 as targets for treatment of liver diseases...

..Our results define a successful therapeutic approach to reduce experimental liver fibrosis by antagonizing Ccl5 receptors...

..Here we assess the intrinsic functions of the chemokine receptor CXCR4 in remodeling after myocardial infarction (MI) using Cxcr4 heterozygous (Cxcr4(+/-)) mice...

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..In these experiments, we observed a decrease of the intrinsic ventricular rate during the first 4 to 5 months when HFES was intermittently shut off...

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..CONCLUSIONS: This novel polylactide stent showed sufficient mechanic stability, and by incorporation of paclitaxel, a significant potential to reduce restenosis development after vascular intervention was seen...

..We investigated whether sCD40L functionally affects peripheral blood-derived angiogenic early outgrowth cells (EOCs) and neointimal remodeling after arterial injury...

..The considerable leap in insight over recent years leads us to anticipate further advances in comprehending the role of chemokines in atherosclerosis, allowing targeted interventions for its prevention and therapy...

..Thus, hypoxia-induced MIF secretion from ECs might play an important role in the recruitment and migration of EPCs to hypoxic tissues such as after ischemia-induced myocardial damage...

..Thus, transmembrane CX3CL1 mediates leukocyte transmigration via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10...

..As an underlying mechanism, KC was involved in promoting CXCR2-mediated endothelial chemotaxis and wound repair...

..In conclusion, repetitive Tx of different cell types after myocardial infarction in rat hearts significantly improved left ventricular function and could represent a feasible option to enhance the benefit of cell therapy...

..Hence, granule proteins modify the monocyte extravasation cascade in a multifaceted manner ensuring the efficiency of these mechanisms...

..In addition, we will discuss recent developments scrutinizing heterophilic interactions of chemokines that have advanced our understanding of how chemokines control vascular inflammatory responses...

..This protocol may represent a basis for standardized analysis and monitoring of these cell subsets to define their normal range and prognostic/diagnostic value in clinical use...

..Efforts in this field might lead to the development of drugs for specific modulation of innate immune functions...

..Although CD73/ecto-5'-nucleotidase has been implicated in maintaining vasoprotection, its role in regulating endothelial adhesion molecule or inflammatory monocyte recruitment (eg, in the context of vascular injury) remains to be defined...

..CONCLUSION: Transplantation of fetal cardiomyocytes results in improvement of left ventricular function. The addition of VEGF does not contribute to further improvement of left ventricular function and angiogenesis in the present model...

..This contribution appears to be attributable to SDF-1alpha-dependent recruitment of circulating SMC progenitor cells...

..Lysophosphatidic acid (LPA) induces CXCL12 and neointimal accumulation of smooth muscle cells (SMCs) in uninjured arteries. Thus, we hypothesize that LPA may regulate CXCL12-mediated vascular remodelling...

..The potential of targeting or exploiting MIF for therapeutic strategies or as a diagnostic marker in the management of cardiovascular diseases or disorders is scrutinized...

..Conclusion: The results underscore an important role of platelets in chronic liver damage and imply a new target for antifibrotic therapies...

..Here, we studied whether treatment with simvastatin after onset of sepsis-induced hemodynamic alterations is beneficial and whether prolonged survival can also be achieved with other statins...

..96 +/- 0.63 mm due to an average intimal hyperplasia area obstruction of 32 +/- 21%, indicating that high-dose dexamethasone-loaded stents do not significantly reduce neointimal proliferation...

..This diversity of chemokine expression and function might lead to the identification of selective therapeutic targets for the prevention and treatment of atherosclerosis...

..However, the specificity of the observed positive clinical effects, the mechanisms regulating the differentiation of EPCs and their homing to sites of injured tissue remain partially unknown at present...

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..If the CCR2 genotype is associated with higher mortality in the general population must be investigated in further studies...

..To discuss crucial cues (chemokines, adhesion molecules and pharmacological means) that guide and control the context-specific mobilization, recruitment and fate of circulating progenitor cells in arterial repair and plaque stability...

..We here review the role of myeloid cells in atherosclerosis as well as the effects of hyperlipidaemia on these cells...

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..Small molecules that block either the receptors or the shedding enzymes of transmembrane chemokines need to be tested in animal models of vascular inflammation...

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..The aim of the study was to analyze whether cadherin- and Rho-family GTPases-mediated dynamic rearrangement of cell-cell adhesion play an important role during human arterial smooth muscle cell (haSMC) migration...

..The combination of clinical data, myocardial reperfusion levels after primary angioplasty for AMI and admission CRP increases the predictive value for subsequent survival...

..The study evaluated the relationship between cardiovascular risk factors (CRF), gene polymorphism, calcification and fibrosis of stenotic aortic valves...

..This finding may provide new physiological/pathological aspects in the communication between cardiomyocytes and other cell types in the myocardium, e.g. fibrocytes, neurocytes or endothelial cells...

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..We thus approached the question of whether treatment with simvastatin might improve cardiovascular function and survival in sepsis...

..The possible significance of these interactions is discussed within the context of vascular inflammation...

..As targeting PMNs without causing serious side effects seems futile, it may be more promising to aim at interfering with subsequent PMN-driven proinflammatory events...

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..Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue...

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..To stimulate further investigations about the contribution of these myeloid cells, we highlight the current mechanistic understanding by which these cells tune atherosclerosis...

..This review discusses recent advances in the field, highlights novel opportunities for therapeutic intervention, and considers both the advantages and disadvantages of intervening in the chemokine system...

..These results may help to define optimal therapeutic doses of pioglitazone for improving endothelial dysfunction...

..Migratory capacity of endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) is a key prerequisite for endothelial repair after denuding injury or endothelial damage...

..Because HIF-1alpha can be activated under normoxic conditions in smooth muscle cells (SMCs) by platelet products, we investigated the role of HIF-1alpha in SDF-1alpha-mediated neointima formation after vascular injury...

..This role of activated platelets in atherosclerosis is attributed to platelet P-selectin-mediated delivery of platelet-derived proinflammatory factors to monocytes/leukocytes and the vessel wall...

..Taken together, chondroitin sulfate A released from platelets appears to act as an important regulatory molecule for cellular responses to chemokines...

..8517 to 0.8908. Therefore, the technical setting described here offers a high-performance and clinically oriented EPC determination strategy in human peripheral blood...