Research Area G: The endocrine-vascular interface: metabolic signals, adipokines, and platlets
| Research Area Leaders | |
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Institute for Vascular Signalling Goethe-University Frankfurt Theodor-Stern-Kai 7 60590 Frankfurt/Main |
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Department of Biochemistry Justus-Liebig University Giessen Friedrichstrass 24 35392 Giessen |
| Faculty involved | |||
|---|---|---|---|
| B. Brüne | S. Dimmeler | J. Eble | B. Fisslthaler |
| I. Fleming | A. Günther | R. Henschler | S. Kanse |
| U. Müller-Ladner | S. Offermanns | J. Pfelschifter | M. Potente |
| K.T. Preissner | V. Randriamboavonjy | S. Rohrbach | D. Sedding |
| C. Urbich | A. Weigert | N. Wettschureck | |
Summary
Altered metabolism, especially in the context of the “metabolic syndrome”, is linked to the accelerated development of cardiovascular disease and atherothrombosis. This condition affects an ever increasing proportion of the population and is expected to reach epidemic proportions in the next 20 years, making patient treatment of major socio-economic importance. However, the cellular metabolites and signalling pathways and the humoral factors (microRNA, adipokines, cytokines and fatty acid-derived mediators) that are the causal links between disturbed metabolic states and the development of cardiovascular disease and atherothrombosis remain to be elucidated. Area G focuses on the endocrine-vascular interface and will concentrate on crosstalk between the vasculature and endogenous metabolic signals, adipokines, platelets, microparticles and platelet-conjugated cellular complexes. Disturbances in vascular homeostasis will be assessed in an integrated approach involving metabolomic and proteomic analyses as well as animal disease models (including genetically altered mice). The overall aims are to elucidate novel causative components and the mechanisms by which they contribute to the onset and progression of the cardio-pulmonary consequences of the metabolic syndrome, as well as to identify new molecular targets for drug therapy.
Most relevant publications of the Research Area G
1. Guarani V, Deflorian G, Franco CA, Krüger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473:234-38, 2011
2. Jordan SD, Krüger M, Willmes DM, Redemann N, Wunderlich FT, Kashkar H, Olkonen VM, Braun T, Böttger T, Seibler J, Brüning JC. Obesity-Induced Overexpression of miRNA-143 Causes Oxsterol-Binding-Protein-Dependent AKT Inhibition. Nat Cell Biol 13:434-46, 2011
3. Li L, Pan R, Li R, Niemann B, Aurich AC, Chen Y, Rohrbach S. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: intact adipocytokine signaling is required. Diabetes 60:157-67, 2011
4. Lukasova M, Malaval C, Gille A, Kero J, Offermanns S. Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J Clin Invest 121:1163-73, 2011
5. Niemann B, Chen Y, Teschner, M, Li L, Silber RE, Rohrbach S. Obesity induces signs of premature cardiac aging in younger patients: Role of mitochondria. J Am Coll Cardiol 57:577-85, 2011
6. Ahmed K, Tunaru S, Tang C, Müller M, Gille A, Sassmann A, Hanson J, Offermanns S. An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab 11:311-19, 2010
7. Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Röxe T, Müller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res 107:677-84, 2010
8. Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, Offermanns S. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J Clin Invest 120:2910-19, 2010
9. Queisser MA, Yao D, Geisler S, Hammes HP, Lochnit G, Schleicher ED, Brownlee M, Preissner KT. Hyperglycemia impairs proteasome function by methylglyoxal. Diabetes 59:670-78, 2010
10. Randriamboavonjy V, Isaak J, Fromel T, Viollet B, Fisslthaler B, Preissner KT, Fleming I. AMPKalpha2 subunit is involved in platelet signaling, clot retraction, and thrombus stability. Blood 116:2134-40, 2010
11. Sassmann A, Gier B, Gröne HJ, Drews G, Offermanns S, Wettschureck N. The Gq/G11-mediated signaling pathway is critical for autocrine potentiation of insulin secretion in mice. J Clin Invest 120:2184-93, 2010
12. Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324:1710-13, 2009
13. Herr B, Zhou J, Werno C, Menrad H, Namgaladze D, Weigert A, Dehne N, Brüne B. The supernatant of apoptotic cells causes transcriptional activation of hypoxia-inducible factor- 1alpha in macrophages via sphingosine-1-phosphate and transforming growth factor-ß. Blood 114:2140-48, 2009
14. Herroeder S, Reichardt P, Sassmann A, Zimmermann B, Jaeneke D, Hoeckner J, Hollmann MW, Fischer KD, Vogt S, Grosse R, Hogg N, Gunzer M, Offermanns S, Wettschureck N. Guanine nucleotide-binding proteins of the G12 family shape immune functions by controlling CD4+ T cell adhesiveness and motility. Immunity 30:708-20, 2009
15. Korhonen H, Fisslthaler B, Moers A, Wirth A, Habermehl D, Wieland T, Schütz G, Wettschureck N, Fleming I, Offermanns S. Anaphylactic shock depends on endothelial Gq/G11. J Exp Med 206:411-20, 2009
16. Lefèvre S, Knedla A, Tennie C, Kampmann A, Wunrau C, Dinser R, Korb A, Schnäker EM, Tarner IH, Robbins PD, Evans CH, Stürz H, Steinmeyer J, Gay S, Schölmerich J, Pap T, Müller-Ladner U, Neumann E. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nature Med 15:1414-20, 2009
17. Prokopi M, Pula G, Mayr U, Devue C, Gallagher J, Xiao Q, Boulanger CM, Westwood N, Urbich C, Willeit J, Steiner M, Breuss J, Xu Q, Kiechl S, Mayr M. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood 114:723-32, 2009
18. Shibamiya A, Hersemeyer K, Schmidt Wöll T, Sedding D, Daniel JM, Bauer S, Koyama T, Preissner KT, Kanse SM. A key role for Toll-like receptor-3 in disrupting the hemostasis balance on endothelial cells. Blood 113:714-22, 2009
19. Urbich C, Rössig L, Kaluza D, Potente M, Boeckel JN, Knau A, Diehl F, Geng JG, Hofmann WK, Zeiher AM, Dimmeler S. HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells. Blood 113:5669-79, 2009
20. Wygrecka M, Marsh LM, Morty RE, Henneke I, Guenther A, Lohmeyer J, Markart P, Preissner KT. Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung. Blood 113:5588-98, 2009
21. Fisslthaler B, Loot AE, Mohamed A, Busse R, Fleming I. Inhibition of endothelial nitric oxide synthase activity by proline-rich tyrosine kinase 2 in response to fluid shear stress and insulin. Circ Res. 102:1520-28, 2008
22. Krüger M, Kratchmarova I, Blagoev B, Tseng YH, Kahn CR, Mann M. Dissection of the insulin signaling pathway via quantitative phosphoproteomics. Proc Natl Acad Sci USA 105:2451-6, 2008
23. Martin M*, Potente M*, Janssens V, Vertommen D, Twizere JC, Rider MH, Goris J, Dimmeler S, Kettmann R, Dequiedt F. Protein phosphatase 2A controls the activity of histone deacetylase 7 during T cell apoptosis and angiogenesis. Proc Natl Acad Sci USA 105:4727-32, 2008 *contributed equally
24. Randriamboavonjy V, Pistrosch F, Bölck B, Schwinger RH, Dixit M, Badenhoop K, Cohen RA, Busse R, Fleming I. Platelet SERCA-2 and μ-calpain activity are altered in type 2 diabetes and restored by rosiglitazone. Circulation 117:52-60, 2008
25. Vadász I, Dada LA, Briva A, Trejo HE, Welch LC, Chen J, Tóth PT, Lecuona E, Witters LA,
Schumacker PT, Chandel NS, Seeger W, Sznajder JI. AMP-activated protein kinase regulatesCO2-induced alveolar epithelial dysfunction in rats and human cells by promoting Na,KATPase endocytosis. J Clin Invest. 118:752-62, 2008
26. Vahkrusheva O, Smolka C, Gajawada P, Kostin S, Böttger T, Kubin T, Braun T, Bober E. Inflammatory cardiomyopathy and premature aging in Sirt7 deficient mice. Circ Res 102:703-10, 2008
27. Wirth A, Benyó Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, Orsy P, Horváth B, Maser-Gluth C, Greiner E, Lemmer B, Schütz G, Gutkind JS, Offermanns S. G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat Med 14:64-68, 2008
28. Kannemeier C, Shibamiya A, Nakazawa F, Trusheim H, Ruppert C, Markart P, Song Y, Tzima E, Kennerknecht E, Niepmann M, von Bruehl ML, Sedding D, Massberg S, Günther A, Engelmann B, Preissner KT. Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 104:6388-93, 2007
29. Potente M, Ghaeni L, Baldessari D, Mostoslavsky R, Rossig L, Dequiedt F, Haendeler J, Mione M, Dejana E, Alt FW, Zeiher AM, Dimmeler S. SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev 21:2644-58, 2007
30. von Knethen A, Soller M, Tzieply N, Weigert A, Johann A M, Jennewein C, Köhl R, Brüne B. PPARγ1 attenuates cytosol to membrane translocation of PKCα to desensitize monocytes/ macrophages. J Cell Biol 176:681-94, 2007