DATABASE-RESEARCH | GROUP OF CLINICAL BIOLOGY RESEARCH | ||||||
Dr. Marten-Steffens | Head of group CV | Research subject | Members of the group |
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Dr. Sabine Steffens Lab. Biologie cardiovasculaire HUG/Spécialités de Médecine La Tulipe, Avenue Roseraie 64 1211 Genève 4 sabine.steffens@unige.ch Tel.: 022 382 72 33 Fax: 022 382 72 45 Comments Pages updated the 17.11.2015 |
Reseach's subject
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Group's publications
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Research's domains
Role of the endocannabinoid system in atherosclerosis
Atherosclerosis is an inflammatory disease characterized by arterial lesions containing cholesterol, immune infiltrates, and connective-tissue elements. It is responsible for the major mortality
causes, i.e. ischemic heart disease and cerebrovascular disease. Atherosclerotic lesions are pathological changes within the arterial wall which may lead to partial obstruction of the vascular lumen
(stenosis). Various risk factors contribute to the initiation and progression of atherosclerosis, and increasing evidence supports a crucial role for inflammatory responses in this
process.
Vascular smooth muscle proliferation and migration are pivotal events in the pathogenesis of atherosclerosis and are directly implicated in the failure of clinical interventions used to treat patients with coronary heart disease. For example, percutaneous transluminal angioplasty is an invasive procedure aimed to repair a stenotic blood vessel by inflating a balloon-tipped catheter at the site of the vascular narrowing followed by an insertion of an expandable wire mesh or hollow perforated tube (stent) into the reconstructed/dilated blood vessel to protect against re-narrowing. It often fails with the time because of the development of restenosis. A growing body of evidence suggests that endocannabinoid signaling plays a critical role in the pathogenesis of atherogenesis and its clinical manifestations. The endocannabinoid system is composed of the two known receptors CB1 and CB2, their endogenous ligands (called endocannabinoids) and enzymes for ligand biosynthesis and inactivation. Rimonabant is the first CB1 antagonist being studied and approved as antiobesity drug in Europe and under review in the United States. Large randomized trials with rimonabant have demonstrated efficacy in treatment of overweight. In addition, multiple other cardiometabolic parameters were improved in the treatment groups, including increased levels of high density lipoprotein cholesterol and reduced triglycerides as well as improved glycemic control in prediabetes patients and in type 2 diabetic patients. Apart from CB1 receptors, CB2 receptors may also play a prominent role in atherosclerosis. Using an experimental mouse model of atherosclerosis, we have recently demonstrated that oral administration of low dose delta-9-Tetrahydrocannabinol (THC) inhibited plaque development, an effect that could be reversed by the CB2 antagonist SR144528. The aim of our research studies is to study the precise role of the endocannabinoid system in the pathogenesis of atherosclerosis, restenosis and myocardial infarction and to test a potential therapeutic benefit of pharmacological intervention. To investigate this, we use both genetic (using receptor-deficient mice) as well as pharmacological (using receptor ligands and antagonists) approaches. Our studies should help to better understand the complex cardiovascular effects of endocannabinoids and clarify their implication in atherosclerosis and its complications. A better knowledge of the endocannabinoid system may help to identify new targets for therapeutic intervention in cardiovascular disease and its complications such as restenosis and myocardial infarction. Our latest findings strongly support this hypothesis and provide the rationale for further investigations. Group's publications Cannabinoid receptor CB2 protects against balloon-induced neointima formation. AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY 2012 vol. 302(5) pp. 1064-1074 MOLICA F, MATTER CM, BURGER F, PELLI G, ZIMMER A, PACHER P, STEFFENS S The activation of the cannabinoid receptor type 2 reduces neutrophilic protease-mediated vulnerability in atherosclerotic plaques. EUROPEAN HEART JOURNAL 2012 vol. 33(7) pp. 846-856 MONTECUCCO F. AND AL. Targeting the endocannabinod system to limit myocardial and cerebral ischemic and reperfusion injury. CURRENT PHARMACEUTICAL BIOTECHNOLOGY 2011 vol. 13(1) pp. 46-58 TUMA R, STEFFENS S Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity. EUROPEAN HEART JOURNAL 2011 vol. 32(11) pp. 1369-1378 QUERCIOLI A. AND AL Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury. JOURNAL OF CLINICAL PATHOLOGY 2011 vol. 64(5) pp. 387-393 FROSSARD JL, LENGLET S, MONTECUCCO F, STEFFENS S, GALAN K, PELLI G, SPAHR L, MACH F, HADENGUE A Mass spectrometry for the evaluation of cardiovascular diseases based on proteomics and lipidomics. THROMBOSIS AND HAEMOSTASIS 2011 vol. 106(1) pp. 20-33 THOMAS A, LENGLET S, MACH F, DEGLON J, MANGIN P, CHAURAND P, WOLFENDER JL, STEFFENS S, STAUB C High-throughput phospholipidic fingerprinting by online desorption of dried spots and quadrupole-linear ion trap mass spectrometry: evaluation of atherosclerosis biomarkers in mouse plasma. ANALYTICAL CHEMISTRY 2010 vol. 82(15) pp. 6687-6694 THOMAS A, DEGLON J, LENGLET S, MACH F, MANGIN P, WOLFENDER JL, STEFFENS S, STAUB C Chemokine CCL5/RANTES inhibition reduces myocardial reperfusion injury in atherosclerotic mice. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 2010 vol. 48(4) pp. 789-798 BRAUNERSREUTHER V, PELLIEUX C, PELLI G, BURGER F, STEFFENS S, MONTESSUIT C, WEBER C, PROUDFOOT A, MACH F, ARNAUD CLAIRE Systemic and intraplaque mediators of inflammation are increased in patients symptomatic for ischemic stroke. STROKE 2010 vol. 41(7) pp. 1394-1404 MONTECUCCO F. AND AL. Regulation and possible role of endocannabinoids and related mediators in hypercholesterolemic mice with atherosclerosis. ATHEROSCLEROSIS. 2009 vol. 205(2) pp. 433-441 MONTECUCCO F, MATIAS I, LENGLET S, PETROSINO S, BURGER F, PELLI G, BRAUNERSREUTHER V, MACH F, STEFFENS S, DI MARZO V CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 2009 vol. 46(5) pp. 612-620 MONTECUCCO F, LENGLET S, BRAUNERSREUTHER V, BURGER F, PELLI G, BERTOLOTTO M, MACH F, STEFFENS S Effect of blockage of the endocannabinoid system by CB(1) antagonism on cardiovascular risk. PHARMACOLOGICAL REPORTS 2009 vol. 61(1) pp. 13-21 MACH F, MONTECUCCO F, STEFFENS S Statins inhibit C-reactive protein-induced chemokine secretion, ICAM-1 upregulation and chemotaxis in adherent human monocytes. RHEUMATOLOGY : OFFICIAL JOURNAL OF THE BRITISH SOCIETY FOR RHEUMATOLOGY 2009 vol. 48(3) pp. 233-242 MONTECUCCO F, BURGER F, PELLI G, POKU NK, PERLIER C, STEFFENS S, MACH F The emerging role of the endocannabinoid system in cardiovascular disease. SEMINARS IN IMMUNOPATHOLOGY 2009 vol. 31(1) pp. 63-77 PACHER P, STEFFENS S The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury. THROMBOSIS AND HAEMOSTASIS 2009 vol. 102(2) pp. 240-247 STEFFENS S, MONTECUCCO F, MACH F CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways.Am J Physiol Heart Circ Physiol AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY 2008 vol. 294(3) pp. 1145-1155 MONTECUCCO F, BURGER F, MACH F, STEFFENS S A novel RANTES antagonist prevents progression of established atherosclerotic lesions in mice. ARTERIOSCLEROSIS, THROMBOSIS AND VASCULAR BIOLOGY 2008 vol. 28(6) pp. 1090-1096 BRAUNERSREUTHER V, STEFFENS S, ARNAUD C, PELLI G, BURGER F, PROUDFOOT A, MACH F Cannabinoid receptors in acute and chronic complications of atherosclerosis. BRITISH JOURNAL OF PHARMACOLOGY 2008 vol. 153(2) pp. 290-298 MACH F, MONTECUCCO F, STEFFENS S Tumor necrosis factor-alpha (TNF-alpha) induces integrin CD11b/CD18 (Mac-1) up-regulation and migration to the CC chemokine CCL3 (MIP-1alpha) on human neutrophils through defined signalling pathways. CELLULAR SIGNALLING 2008 vol. 20(3) pp. 557-568 MONTECUCCO F, STEFFENS S, BURGER F, DA COSTA A, BIANCHI G, BERTOLOTTO M, MACH F, DALLEGRI F, OTTONELLO L Adiponectin and adaptive immunity: linking the bridge from obesity to atherogenesis. CIRCULATION RESEARCH 2008 vol. 102(2) pp. 140-142 STEFFENS S, MACH F C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes. JOURNAL OF LEUKOCYTE BIOLOGY 2008 vol. 84(4) pp. 1109-1119 MONTECUCCO F, STEFFENS S, BURGER F, PELLI G, MONACO C, MACH F The role of the endocannabinoid system in atherosclerosis. JOURNAL OF NEUROENDOCRINOLOGY 2008 vol. 20 pp. 53-57 MACH F, STEFFENS S Insulin resistance: a proinflammatory state mediated by lipid-induced signaling dysfunction and involved in atherosclerotic plaque instability. MEDIATORS OF INFLAMMATION 2008 vol. 2008 pp. 767623-767623 MONTECUCCO F, STEFFENS S, MACH F Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 2007 vol. 27 pp. 373-379 BRAUNERSREUTHER V, ZERNECKE A, ARNAUD C, LIEHN EA, STEFFENS S, SHAGDARSUREN E, BIDZHEKOV K, BURGER F, PELLI G, LUCKOW B, MACH F, WEBER C The immune response is involved in atherosclerotic plaque calcification: could the RANKL/RANK/OPG system be a marker of plaque instability? CLINICAL & DEVELOPMENTAL IMMUNOLOGY 2007 vol. 2007 pp. 75805- MONTECUCCO F, STEFFENS S, MACH F The specific role of chemokines in atherosclerosis THROMBOSIS AND HAEMOSTASIS 2007 vol. 97 pp. 714-721 BRAUNERSREUTHER V, MACH F, STEFFENS S Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages ATHEROSCLEROSIS 2006 vol. 188 pp. 51-58 VEILLARD NR, BRAUNERSREUTHER V, ARNAUD C, BURGER F, PELLI G, STEFFENS S, MACH F Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice CIRCULATION 2006 vol. 114 pp. 1977-1984 STEFFENS S, BURGER F, PELLI G, DEAN Y, ELSON G, KOSCO-VILBOIS M, CHATENOUD L, MACH F Cannabinoid receptors in atherosclerosis CURRENT OPINION IN LIPIDOLOGY 2006 vol. 17(5) pp. 519-526 STEFFENS S, MACH F Drug insight: Immunomodulatory effects of statins--potential benefits for renal patients? NATURE CLINICAL PRACTICE NEPHROLOGY 2006 vol. 2(7) pp. 378-387 STEFFENS S, MACH F Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. ARTERIOSCLEROSIS, THROMBOSIS AND VASCULAR BIOLOGY 2005 vol. 25(6) pp. 1231-1236 ARNAUD CLAIRE, BURGER FABIENNE, STEFFENS S, VEILLARD NIELS, NGUYEN TUAN HUY, MACH FRANCOIS Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo. CIRCULATION 2005 vol. 112(6) pp. 870-878 VEILLARD NIELS, STEFFENS S, PELLI G, LU B, KWAK BR, GERARD C, CHARO IF, MACH F Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. NATURE 2005 vol. 434(7034) pp. 782-786 STEFFENS S, VEILLARD N, ARNAUD C, PELLI G, BURGER F, STAUB C, KARSAK M, ZIMMER A, FROSSARD JL, MACH F Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. ONCOGENE : AN INTERNATIONAL JOURNAL 2005 vol. 24(7) pp. 1231-1243 FISCHER U, STEFFENS S, FRANK S, RAINOV NG, SCHULZE-OSTHOFF K, KRAMM CM Differential expression patterns of proinflammatory and antiinflammatory mediators during atherogenesis in mice ARTERIOSCLEROSIS, THROMBOSIS AND VASCULAR BIOLOGY 2004 vol. 24(12) pp. 2339-2344 VEILLARD NR, STEFFENS S, BURGER F, PELLI G, MACH F Inflammation and Atherosclerosis. HERZ 2004 vol. 29 (8) pp. 741-748 STEFFENS S, MACH F Transduction of human glial and neuronal tumor cells with different lentivirus vector pseudotypes JOURNAL OF NEURO-ONCOLOGY 2004 vol. 70(3) pp. 281-288 STEFFENS S, TEBBETS J, KRAMM CM, LINDEMANN D, FLAKE A, SENA-ESTEVES M Optimized large-scale production of high titer lentivirus vector pseudotypes JOURNAL OF VIROLOGICAL METHODS 2004 vol. 122(2) pp. 131-139 SENA-ESTEVES M, TEBBETS JC, STEFFENS S, CROMBLEHOLME T, FLAKE AW A neuroblastoma-selective suicide gene therapy approach using the tyrosine hydroxylase promoter PEDIATRIC RESEARCH : AN INTERNATIONAL JOURNAL OF CLINICAL, LABORATORY AND DEVELOPMENTAL INVESTIGATION 2004 vol. 56(2) pp. 268-277 STEFFENS S, SANDQUIST A, FRANK S, FISCHER U, LEX C, RAINOV NG, KRAMM CM Research's domains |