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Vascular endothelium

The intact vascular endothelium presents an anti-inflammatory and anticoagulant interface between blood and vessel wall. Inappropriate activation, damage or deficiencies of the endothelium contribute to a large part of morbidity and mortality in humans. Pathologic conditions in which the endothelium plays a key role include cancer, thrombosis, atherosclerosis and sepsis, to mention just a few atherosclerosis being responsible for myocardial infarction, stroke, peripheral artery disease and brain dysfunction. The endothelium can be considered as a paracrine/endocrine tissue. Endothelial cells contain storage granules, called Weibel-Palade bodies, that release their contents in response to a variety of agents such as thrombin, histamine, calcium ionophores or cAMP-enhancing agents. Proteins stored in endothelial cells have profound effects on hemostasis (t-PA, TFPI, von Willebrand factor {vWF}, factor VIII and factor XIII), on vascular tone (endothelin, calcitonin gene-related peptide), and on leukocyte adhesion and migration (P-selectin, interleukin-8, CD63). Activation of endothelial cells by inflammatory mediators modifies the composition of the Weibel-Palade bodies and leads to a more pro-coagulant, pro-inflammatory phenotype.
In recent years it has become evident that the adult organism is able to repair vascular damage or, if required, generate new blood vessels. Central to this is the endothelial progenitor cell, a bone marrow derived cell that circulates in small amounts in adult blood. Circulating progenitor cells may home into sites of vascular damage or infiltrate into regions of ischemia and thereby contribute to the generation of new blood vessels. This may be beneficial in the context of ischemic diseases, but detrimental in the case of malignant diseases.
The main interest of our research group is the development of efficient means to isolate endothelial progenitor cells from adult sources, to investigate approaches to inhibit the inflammatory activation or enhance the anticoagulant potential of these cells. A particular aim is to determine whether endothelial cells can be used to store proteins of therapeutic interest that will be released preferentially when endothelial cells are activated. Central to our research approaches is the use of adenoviral and lentiviral vectors to transiently or stably express therapeutic proteins in endothelial cells. Our approach may lead to a better understanding of the mechanisms underlying vascular disease and the development of therapeutics using unmodified or genetically modified endothelial (progenitor) cells.

Group's publications

Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model.
CANCER GENE THERAPY
2008 vol. 15(10) pp. 685-692
SOLLY F, FISH R, SIMARD B, BOLLE N, KRUITHOF EGBERT, POLACK B, PERNOD GILLES

Endothelial cell activation by immunoglobulins from patients with immune thrombocytopenic purpura or with antiphospholipid syndrome.
HAEMATOLOGIA
2008 vol. 93(4) pp. 635-636
DUNOYER-GEINDRE S, BOEHLEN F, FAVIER R, WAHL D, MUSIAL J, KORTE W, SATTA N, KRUITHOF EGBERT, DE MOERLOOSE P

Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
2008 vol. 6(10) pp. 1796-1803
HULTMAN K, TJÄRNLUND-WOLF A, FISH RJ, WILHELMSSON U, RYDENHAG B, PEKNY M, KRUITHOF EK, JERN C

Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides.
MOLECULAR IMMUNOLOGY
2008 vol. 46(1) pp. 145-157
SATTA N, KRUITHOF EK, REBER G, DE MOERLOOSE P

Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins.
THROMBOSIS AND HAEMOSTASIS
2008 vol. 100(6) pp. 969-975
KRUITHOF EK

Fluvastatin inhibits regulated secretion of endothelial cell von Willebrand factor in response to diverse secretagogues
BIOCHEMICAL JOURNAL
2007 vol. 405 pp. 597-604
FISH RJ, YANG H, VIGLINO C, SCHORER R, DUNOYER-GEINDRE S, KRUITHOF EKO

The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies
BLOOD
2007 vol. 109 pp. 1507-1514
SATTA N, DUNOYER-GEINDRE S, REBER G, FISH RJ, BOEHLEN F, KRUITHOF EKO, DE MOERLOOSE P

Gene conversion limits divergence of mammalian TLR1 and TLR6
BMC EVOLUTIONARY BIOLOGY [COMPUTER FILE]
2007 vol. 7 pp. 148-148
KRUITHOF EK, SATTA-POSCHUNG N, LIU JW, DUNOYER-GEINDRE S, FISH RJ

Characterization of endothelial-like cells derived from human mesenchymal stem cells
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
2007 vol. 5 pp. 826-834
LIU JW, DUNOYER-GEINDRE S, SERRE-BEINIER V, MAI G, LAMBERT JF, FISH RJ, PERNOD G, BUEHLER L, BOUNAMEAUX H, KRUITHOF EKO

Immunization of LDL receptor-deficient mice with beta(2)-glycoprotein 1 or human serum albumin induces a more inflammatory phenotype in atherosclerotic plaques
THROMBOSIS AND HAEMOSTASIS
2007 vol. 97 pp. 129-138
DUNOYER-GEINDRE S, KWAK BR, PELLI G, ROTH I, SATTA N, FISH RJ, REBER G, MACH F, KRUITHOF EKO, DE MOERLOOSE P

Evidence for serpinB2-independent protection from TNF-alpha-induced apoptosis
EXPERIMENTAL CELL RESEARCH
2006 vol. 312 pp. 350-361
FISH RJ, KRUITHOF EKO

Promoter dependence of transgene expression by lentivirus-transduced human blood-derived endothelial progenitor cells
STEM CELLS
2006 vol. 24 pp. 199-208
LIU JW, PERNOD G, DUNOYER-GEINDRE S, FISH RJ, YANG H, BOUNAMEAUX H, KRUITHOF EKO

Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in human endothelial cells both in vitro and in vivo
BLOOD
2002 vol. 99 pp. 3637-3645
HUBER D, CRAMER EM, KAUFMANN JE, MEDA P, MASSE JM, KRUITHOF EK, VISCHER UM

Synergistic induction of tissue-type plasminogen activator (tPA) by vascular endothelial growth factor and basic fibroblast growth factor and localization of tPA to Weibel-Palade bodies in bovine micr ovascular endothelial cells
THROMBOSIS AND HAEMOSTASIS
2001 vol. 86 pp. 702-709
PEPPER MS, ROSNOBLET C, DI SANZA C, KRUITHOF EGBERT

Evidence for a co-receptor for the cellular degradation of free and inhibitor-bound tissue-type plasminogen activator
THROMBOSIS AND HAEMOSTASIS
2000 vol. 83 pp. 290-296
CAMANI C, GAVIN O, KRUITHOF EGBERT

storage of tissue-type plasminogen activator in Weibel-Palade bodies of human endothelial cells
ARTERIOSCLEROSIS, THROMBOSIS AND VASCULAR BIOLOGY
1999 vol. 19 pp. 1796-1803
ROSNOBLET CORINNE, VISCHER ULRICH, GERARD RD, IRMINGER JEAN-CLAUDE, HALBAN PHILIPPE A., KRUITHOF EGBERT

The coagulation and fibrinolytic responses of baboons to experimental disseminated intravascular coagulation. Effect of interleukin-6.
THROMBOSIS AND HAEMOSTASIS
1997 vol. 77 pp. 905-910
KRUITHOF EGBERT, MESTRIES JC, GASCON MARIE-PAUL, YTHIER A

Research's domains




DATABASE-RESEARCH	GROUP OF CLINICAL BIOLOGY RESEARCH

Egbert KRUITHOF	Head of group CV	Research subject	Members of the group


	Links about the group Prof. Egbert KRUITHOF HUG/Spécialités de médecine Service d'Angiologie Hémostase Rue Gabrielle-Perret-Gentil 4 1211 Genève 14 Suisse Egbert.Kruithof@hcuge.ch Tel.: 022/372.97.58 Fax: 022/ 372 92 99 Comments Pages updated the 17.11.2015		Reseach's subject \| Group's publications \| Research's domains Vascular endothelium The intact vascular endothelium presents an anti-inflammatory and anticoagulant interface between blood and vessel wall. Inappropriate activation, damage or deficiencies of the endothelium contribute to a large part of morbidity and mortality in humans. Pathologic conditions in which the endothelium plays a key role include cancer, thrombosis, atherosclerosis and sepsis, to mention just a few atherosclerosis being responsible for myocardial infarction, stroke, peripheral artery disease and brain dysfunction. The endothelium can be considered as a paracrine/endocrine tissue. Endothelial cells contain storage granules, called Weibel-Palade bodies, that release their contents in response to a variety of agents such as thrombin, histamine, calcium ionophores or cAMP-enhancing agents. Proteins stored in endothelial cells have profound effects on hemostasis (t-PA, TFPI, von Willebrand factor {vWF}, factor VIII and factor XIII), on vascular tone (endothelin, calcitonin gene-related peptide), and on leukocyte adhesion and migration (P-selectin, interleukin-8, CD63). Activation of endothelial cells by inflammatory mediators modifies the composition of the Weibel-Palade bodies and leads to a more pro-coagulant, pro-inflammatory phenotype. In recent years it has become evident that the adult organism is able to repair vascular damage or, if required, generate new blood vessels. Central to this is the endothelial progenitor cell, a bone marrow derived cell that circulates in small amounts in adult blood. Circulating progenitor cells may home into sites of vascular damage or infiltrate into regions of ischemia and thereby contribute to the generation of new blood vessels. This may be beneficial in the context of ischemic diseases, but detrimental in the case of malignant diseases. The main interest of our research group is the development of efficient means to isolate endothelial progenitor cells from adult sources, to investigate approaches to inhibit the inflammatory activation or enhance the anticoagulant potential of these cells. A particular aim is to determine whether endothelial cells can be used to store proteins of therapeutic interest that will be released preferentially when endothelial cells are activated. Central to our research approaches is the use of adenoviral and lentiviral vectors to transiently or stably express therapeutic proteins in endothelial cells. Our approach may lead to a better understanding of the mechanisms underlying vascular disease and the development of therapeutics using unmodified or genetically modified endothelial (progenitor) cells. Group's publications Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model. CANCER GENE THERAPY 2008 vol. 15(10) pp. 685-692 SOLLY F, FISH R, SIMARD B, BOLLE N, KRUITHOF EGBERT, POLACK B, PERNOD GILLES Endothelial cell activation by immunoglobulins from patients with immune thrombocytopenic purpura or with antiphospholipid syndrome. HAEMATOLOGIA 2008 vol. 93(4) pp. 635-636 DUNOYER-GEINDRE S, BOEHLEN F, FAVIER R, WAHL D, MUSIAL J, KORTE W, SATTA N, KRUITHOF EGBERT, DE MOERLOOSE P Retinoids and activation of PKC induce tissue-type plasminogen activator expression and storage in human astrocytes. JOURNAL OF THROMBOSIS AND HAEMOSTASIS 2008 vol. 6(10) pp. 1796-1803 HULTMAN K, TJÄRNLUND-WOLF A, FISH RJ, WILHELMSSON U, RYDENHAG B, PEKNY M, KRUITHOF EK, JERN C Induction of TLR2 expression by inflammatory stimuli is required for endothelial cell responses to lipopeptides. MOLECULAR IMMUNOLOGY 2008 vol. 46(1) pp. 145-157 SATTA N, KRUITHOF EK, REBER G, DE MOERLOOSE P Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins. THROMBOSIS AND HAEMOSTASIS 2008 vol. 100(6) pp. 969-975 KRUITHOF EK Fluvastatin inhibits regulated secretion of endothelial cell von Willebrand factor in response to diverse secretagogues BIOCHEMICAL JOURNAL 2007 vol. 405 pp. 597-604 FISH RJ, YANG H, VIGLINO C, SCHORER R, DUNOYER-GEINDRE S, KRUITHOF EKO The role of TLR2 in the inflammatory activation of mouse fibroblasts by human antiphospholipid antibodies BLOOD 2007 vol. 109 pp. 1507-1514 SATTA N, DUNOYER-GEINDRE S, REBER G, FISH RJ, BOEHLEN F, KRUITHOF EKO, DE MOERLOOSE P Gene conversion limits divergence of mammalian TLR1 and TLR6 BMC EVOLUTIONARY BIOLOGY [COMPUTER FILE] 2007 vol. 7 pp. 148-148 KRUITHOF EK, SATTA-POSCHUNG N, LIU JW, DUNOYER-GEINDRE S, FISH RJ Characterization of endothelial-like cells derived from human mesenchymal stem cells JOURNAL OF THROMBOSIS AND HAEMOSTASIS 2007 vol. 5 pp. 826-834 LIU JW, DUNOYER-GEINDRE S, SERRE-BEINIER V, MAI G, LAMBERT JF, FISH RJ, PERNOD G, BUEHLER L, BOUNAMEAUX H, KRUITHOF EKO Immunization of LDL receptor-deficient mice with beta(2)-glycoprotein 1 or human serum albumin induces a more inflammatory phenotype in atherosclerotic plaques THROMBOSIS AND HAEMOSTASIS 2007 vol. 97 pp. 129-138 DUNOYER-GEINDRE S, KWAK BR, PELLI G, ROTH I, SATTA N, FISH RJ, REBER G, MACH F, KRUITHOF EKO, DE MOERLOOSE P Evidence for serpinB2-independent protection from TNF-alpha-induced apoptosis EXPERIMENTAL CELL RESEARCH 2006 vol. 312 pp. 350-361 FISH RJ, KRUITHOF EKO Promoter dependence of transgene expression by lentivirus-transduced human blood-derived endothelial progenitor cells STEM CELLS 2006 vol. 24 pp. 199-208 LIU JW, PERNOD G, DUNOYER-GEINDRE S, FISH RJ, YANG H, BOUNAMEAUX H, KRUITHOF EKO Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in human endothelial cells both in vitro and in vivo BLOOD 2002 vol. 99 pp. 3637-3645 HUBER D, CRAMER EM, KAUFMANN JE, MEDA P, MASSE JM, KRUITHOF EK, VISCHER UM Synergistic induction of tissue-type plasminogen activator (tPA) by vascular endothelial growth factor and basic fibroblast growth factor and localization of tPA to Weibel-Palade bodies in bovine micr ovascular endothelial cells THROMBOSIS AND HAEMOSTASIS 2001 vol. 86 pp. 702-709 PEPPER MS, ROSNOBLET C, DI SANZA C, KRUITHOF EGBERT Evidence for a co-receptor for the cellular degradation of free and inhibitor-bound tissue-type plasminogen activator THROMBOSIS AND HAEMOSTASIS 2000 vol. 83 pp. 290-296 CAMANI C, GAVIN O, KRUITHOF EGBERT storage of tissue-type plasminogen activator in Weibel-Palade bodies of human endothelial cells ARTERIOSCLEROSIS, THROMBOSIS AND VASCULAR BIOLOGY 1999 vol. 19 pp. 1796-1803 ROSNOBLET CORINNE, VISCHER ULRICH, GERARD RD, IRMINGER JEAN-CLAUDE, HALBAN PHILIPPE A., KRUITHOF EGBERT The coagulation and fibrinolytic responses of baboons to experimental disseminated intravascular coagulation. Effect of interleukin-6. THROMBOSIS AND HAEMOSTASIS 1997 vol. 77 pp. 905-910 KRUITHOF EGBERT, MESTRIES JC, GASCON MARIE-PAUL, YTHIER A Research's domains