I Fleming


Affiliation: Frankfurt am Main
Country: Germany


  1. Randriamboavonjy V, Kyselova A, Fleming I. Redox-regulation of calpains: consequences on vascular function. Antioxid Redox Signal. 2018;: pubmed publisher
  2. Zippel N, Loot A, Stingl H, Randriamboavonjy V, Fleming I, Fisslthaler B. Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation. Int J Mol Sci. 2018;19: pubmed publisher
    ..The results of this study indicate that AMPKα1 targets the inhibitory phosphorylation Thr495 site in the calmodulin-binding domain of eNOS to attenuate basal NO production and phenylephrine-induced vasoconstriction. ..
  3. Randriamboavonjy V, Fleming I. Platelet communication with the vascular wall: role of platelet-derived microparticles and non-coding RNAs. Clin Sci (Lond). 2018;132:1875-1888 pubmed publisher
    ..The aim of this review is to discuss the role of platelet-derived factors, adhesion molecules as well as RNAs as mediators of the cross-talk between platelets and the vessel wall. ..
  4. Fleming I. The pharmacology of the cytochrome P450 epoxygenase/soluble epoxide hydrolase axis in the vasculature and cardiovascular disease. Pharmacol Rev. 2014;66:1106-40 pubmed publisher
    ..Moreover, inhibitors of the soluble epoxide hydrolase that increase epoxide but decrease diol levels have potential for the treatment of the metabolic syndrome. ..
  5. Hu J, Frömel T, Fleming I. Angiogenesis and vascular stability in eicosanoids and cancer. Cancer Metastasis Rev. 2018;37:425-438 pubmed publisher
    ..This review highlights current knowledge on the function of PUFA metabolites generated by the CYP/sEH pathway in angiogenesis and vascular stability as well as their potential involvement in cancer development. ..
  6. Bibli S, Hu J, Sigala F, Wittig I, Heidler J, Zukunft S, et al. Cystathionine ? Lyase Sulfhydrates the RNA Binding Protein HuR to Preserve Endothelial Cell Function and Delay Atherogenesis. Circulation. 2018;: pubmed publisher
    ..However, as a consequence of vascular inflammation the beneficial actions of CSE-derived H2S are lost due to the phosphorylation and inhibition of the enzyme. ..
  7. Fleming I, Bauersachs J, Schafer A, Scholz D, Aldershvile J, Busse R. Isometric contraction induces the Ca2+-independent activation of the endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1999;96:1123-8 pubmed
    ..Thus, isometric contraction activates eNOS via a Ca2+-independent, tyrosine kinase inhibitor-sensitive pathway and, like shear stress, seems to be an independent determinant of mechanically induced NO formation. ..
  8. Kohlstedt K, Trouvain C, Frömel T, Mudersbach T, Henschler R, Fleming I. Role of the angiotensin-converting enzyme in the G-CSF-induced mobilization of progenitor cells. Basic Res Cardiol. 2018;113:18 pubmed publisher
    ..These results indicate that ACE expression/phosphorylation in the bone-marrow niche interface negatively regulates G-CSF-induced signaling and HPC mobilization. ..
  9. Fleming I, Busse R. Endothelium-derived epoxyeicosatrienoic acids and vascular function. Hypertension. 2006;47:629-33 pubmed

More Information


  1. Fleming I, Mohamed A, Galle J, Turchanowa L, Brandes R, Fisslthaler B, et al. Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCalpha. Cardiovasc Res. 2005;65:897-906 pubmed
  2. Fleming I. Vascular cytochrome p450 enzymes: physiology and pathophysiology. Trends Cardiovasc Med. 2008;18:20-5 pubmed publisher
    ..Epoxyeicosatrienoic acids are recognized as lipid mediators that participate in vascular signaling processes such as the acute regulation of vascular tone and the processes of inflammation and angiogenesis. ..
  3. Mangels N, Awwad K, Wettenmann A, Dos Santos L, Frömel T, Fleming I. The soluble epoxide hydrolase determines cholesterol homeostasis by regulating AMPK and SREBP activity. Prostaglandins Other Lipid Mediat. 2016;125:30-9 pubmed publisher
    ..Thus, AMPK activation and subsequent inhibition of SREBP can account for the altered expression of lipid metabolizing enzymes in sEH(-/-) mice. ..
  4. Fleming I. Molecular mechanisms underlying the activation of eNOS. Pflugers Arch. 2010;459:793-806 pubmed publisher
    ..This review summarizes some of the recent findings relating to the molecular events regulating eNOS activity. ..
  5. Awwad K, Hu J, Shi L, Mangels N, Abdel Malik R, Zippel N, et al. Role of secreted modular calcium-binding protein 1 (SMOC1) in transforming growth factor β signalling and angiogenesis. Cardiovasc Res. 2015;106:284-94 pubmed publisher
    ..These results indicate that SMOC1 is an ALK5 antagonist produced by endothelial cells that tips TGF-β signalling towards ALK1 activation, thus promoting endothelial cell proliferation and angiogenesis. ..
  6. Shi L, Kojonazarov B, Elgheznawy A, Popp R, Dahal B, Böhm M, et al. miR-223-IGF-IR signalling in hypoxia- and load-induced right-ventricular failure: a novel therapeutic approach. Cardiovasc Res. 2016;111:184-93 pubmed publisher
  7. Siragusa M, Fleming I. The eNOS signalosome and its link to endothelial dysfunction. Pflugers Arch. 2016;468:1125-37 pubmed publisher
    ..The mechanisms underlying eNOS uncoupling and clinically relevant strategies that were adopted to influence them are also discussed. ..
  8. Abdel Malik R, Zippel N, Frömel T, Heidler J, Zukunft S, Walzog B, et al. AMP-Activated Protein Kinase α2 in Neutrophils Regulates Vascular Repair via Hypoxia-Inducible Factor-1α and a Network of Proteins Affecting Metabolism and Apoptosis. Circ Res. 2017;120:99-109 pubmed publisher
    ..The activation of AMPKα2 in neutrophils is a decisive event in the initiation of vascular repair after ischemia. ..
  9. Fleming I. The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling. Vascul Pharmacol. 2016;86:31-40 pubmed publisher
    ..This review outlines the evidence for a physiological role for EETs in the regulation of vascular homeostasis. ..
  10. Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, et al. Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res. 2015;117:157-65 pubmed publisher
    ..Thus, calpain inhibition may be one means of normalizing platelet miRNA processing as well as platelet function in diabetes mellitus. ..
  11. Hu J, Geyer A, Dziumbla S, Awwad K, Zeldin D, Schunck W, et al. Role of Müller cell cytochrome P450 2c44 in murine retinal angiogenesis. Prostaglandins Other Lipid Mediat. 2017;133:93-102 pubmed publisher
    ..The enhanced endothelial cell proliferation and Notch inhibition seen in retinas from Cyp2c44-deficient mice indicate a role for Cyp2c44-derived lipid mediators in physiological angiogenesis. ..
  12. Zippel N, Ding Y, Fleming I. A Modified Aortic Ring Assay to Assess Angiogenic Potential In Vitro. Methods Mol Biol. 2016;1430:205-19 pubmed publisher
    ..This model can be modified to include genetic manipulation and can be used to assess the pro- or anti-angiogenic effects of compounds in a relatively controlled system. ..
  13. Fleming I, Rueben A, Popp R, Fisslthaler B, Schrodt S, Sander A, et al. Epoxyeicosatrienoic acids regulate Trp channel dependent Ca2+ signaling and hyperpolarization in endothelial cells. Arterioscler Thromb Vasc Biol. 2007;27:2612-8 pubmed
    ..Here we address the mechanisms by which cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) contribute to this effect in native and cultured endothelial cells...
  14. Fleming I, Fisslthaler B, Dixit M, Busse R. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. J Cell Sci. 2005;118:4103-11 pubmed
  15. Fleming I, Schulz C, Fichtlscherer B, Kemp B, Fisslthaler B, Busse R. AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of the nitric oxide synthase in human platelets. Thromb Haemost. 2003;90:863-71 pubmed
  16. Fleming I, Fisslthaler B, Dimmeler S, Kemp B, Busse R. Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001;88:E68-75 pubmed
    ..Moreover, the dephosphorylation of Thr(495) by PP1 precedes the phosphorylation of Ser(1177) by CaMKII. The full text of this article is available at http://www.circresaha.org. ..