MANN Giovanni

Contacts

Contacting person:  Giovanni E. Mann
e-mail: giovanni.mann@kcl.ac.uk;
Full address: Cardiovascular Division
British Heart Foundation Centre of Excellence
School of Medicine
King’s College London
Franklin-Wilkins Building (Rm. 3.01)
150 Stamford Street
London SE1 9NH, U.K.
Group members

Prof Giovanni E. Mann (Professor of Vascular Physiology)
Dr Richard C.M. Siow (Senior Lecturer in Physiology)
Prof Richard J. Naftalin (Emeritus Professor, KCL)
Dr Paul A. Fraser (Emeritus, Senior Lecturer, KCL)
Dr Ron Jacob (Senior Lecturer in Physiology)
Dr Sarah Chapple (Postdoc, Heart Research UK)
Dr Alessio Alfieri (Postdoc, Henry Smith Charity)
Xinghua Cheng (PhD, China Scholarship Council)
Tabasum Mughal (PhD, British Heart Foundation, with Dr Siow)
Fiona Shaunessey (PhD, EPSRC, with Dr Siow)
Shane McSweeney (PhD, BBSRC-CASE, with Dr Siow)
Salil Srivastava (PhD, British Heart Foundation)
Bijal Patel (PhD, British Heart Foundation)

Research Visitors:
Prof Tetsuro Ishii (Univ. Tsukuba, Japan)
Prof Claudio Mendes-Ribeiro (UERJ, Rio de Janeiro, Brazil)
Dr Daniela Mastronicol (Univ. Roma, Italy)

Research interests

Prof Mann’s Vascular Biology Group is investigating the signalling cascades involved the transcriptional activation of antioxidant defence genes in endothelial and smooth muscle cells in oxidative stress. We are particularly interested in HNE induced redox signalling in endothelial and smooth muscle cells exposed to oxidative stress in diseases such as atherosclerosis, pre-eclampsia, chronic renal failure and diabetes, focusing on the redox sensitive transcription factor Nrf2 as a major regulator of antioxidant responsive element (ARE) mediated gene expression.

Techniques

Lucigenin/L012 chemiluminescence of ROS generation Immunoblotting Quantitative real time PCR Integrative physiology – surgical expertise Radiotelemetry Fluorescence microscopy Luminescence measurements of ROS generation Immunoblotting qRT-PCR Proteomics (in collaboration with colleagues in the Centre) see above

Selected references

Siow, R.C.M. & Mann, G.E. (2010). Dietary isoflavones and vascular protection: activation of cellular antioxidant defenses by SERMs or hormesis? Mol. Aspects Med. Sep 10. [Epub ahead of print]

Cheng, X., Siow, R.C.M., Mann, G.E. (2010). Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the Nrf2-Keap1 defense pathway. Antiox. Redox Signaling 2010 Aug 20. [Epub ahead of print] doi:10.1089/ars.2010.3283

Negre-Salvayre, A., Auge, N., Ayala, V., Basaga, H.,Boada, J., Brenke, R.,Chapple, S., Cohen, G., Feher, J., Grune, T., Lengyel, G., Mann, G.E., Pamplona, R., Poli, G., Portero-Otin, M., Riahi, Y., Salvayre, R., Sasson, S., Serrano, J., Shamni, O., Siems, W., Siow, R.C., Wiswedel, I., Zarkovic, K., Zarkovic, N. (2010). Pathological Aspects of Lipid Peroxidation. Free Radical Res. 44: 1125-1171.

Warboys, C.M., Berson, R.E., Mann, G.E., Pearson, J.D. & Weinberg, P.D. (2010). Acute and chronic exposure to shear stress have opposite effects on endothelial permeability to macromolecules. Am. J. Physiol. Heart Circ. Physiol. 298:H1850-H1858.

He, M., Siow, R.C.M., Sugden, D., Gao, L., Cheng, X. & Mann, G.E. (2010). Induction of HO-1 and redox signaling in endothelial cells by advanced glycation end products: a role for the Nrf2-Keap1 pathway in vascular protection in diabetes. Nutr. Metab. Cardiovasc. Dis., in press, doi.org/10.1016/j.numecd.2009.12.008.

Sugimoto, R., Warabi, E., Katayanagi, S., Sakai, S., Uwayama, J., Yanagawa, T., Watanabe, A., Harada, H., Kitamura, K., Noguti, N., Yoshida, H., Siow, R.C.M., Mann, G.E. & Ishii, T. (2009). Enhanced neointimal hyperplasia and carotid artery remodeling in p62/A170 deficient mice: novel role for p62/A170 as a repressor of smooth muscle proliferation. J. Cell. Mol. Med. 14:1546-1554.

Mann, G.E., Bonacasa, B., Ishii, T. & Siow, R.C.M. (2009). Targeting the redox sensitive Nrf2-Keap1 defense pathway in cardiovascular disease: protection afforded by dietary isoflavones. Curr. Opin. Pharmacol. 9:139-145 Gao, L. & Mann, G.E. (2009). Vascular NADPH oxidase activation in diabetes: a double-edged sword in redox signaling. Cardiovasc. Res. 82:9-20

Steinert, J.R., Wyatt, A.W., Jacob, R. & Mann, G.E. (2009). Redox modulation of Ca2+ signaling in human endothelial and smooth muscle cells in pre-eclampsia. Antiox. Redox Signaling 11:1149-1163

Siow, R.C.M. & Mann, G.E. (2009). Dietary isoflavones: cardiovascular actions and activation of cellular signaling pathways. Plant Phenolics And Human Health: Biochemistry, Nutrition And Pharmacology, ed. Fraga CG, pp. 249-264. A John Wiley & Sons, Inc.

Churchman, A.T., Anwar, A., Li, F.Y., Sato, H., Ishii, T., Mann, G.E. & Siow, R.C.M. (2009). Activation of the Nfr2 pathway in human smooth muscle cells: a new vascular target of transforming growth factor-1. J. Cell. Mol. Med. 13:2282-2292.

Mendes-Ribeiro, A.C., Mann, G.E., de Meirelles L.R., Moss, M.B., Matsuura, C. & Brunini, T.M.C. (2009). The role of exercise on L-arginine-nitric oxide pathway in chronic heart failure. The Open Biochemistry J. 3: 55-65.

de Meirelles, L.R., Mendes-Ribeiro, A.C., Mendes, M.A.P, da Silva, M.N., Ellory, J.C., Mann, G.E. & Brunini T.M.C. (2009). Chronic exercise reduces platelet activation in hypertension: upregulation of the L-arginine-nitric oxide pathway. Scand. J. Med. Sci. Sports 19:67-74

Mendes-Ribeiro, A.C., Moss, M.B., Siqueira, M.A., Moraes, T.L., Ellory, J.C., Mann, G.E. & Brunini, T.M. (2008). Dengue fever activates the L-arginine-nitric oxide pathway: an explanation for reduced aggregation of human platelets. Clin. Exp. Pharmacol. Physiol 35:1143-1146

Rodford, J.L., Torrens, C., Siow, R.C.M., Mann, G.E., Hanson M.A. & Clough GF (2008). Endothelial dysfunction and reduced antioxidant protection in an animal model of the developmental origins of cardiovascular disease. J. Physiol. 586.19:4709-4720

Brunini, T.M.C., Mendes-Ribeiro, A.C., Ellory, J.C. & Mann, G.E. (2007). Platelet nitric oxide synthesis in malnutrition and uremia: a role for L-arginine supplementation in vascular protection? Cardiovasc. Res. 73:359-367 D

uggan, S., Lindstrom, T., Iglesias, T., Bennett, P.R., Mann, G.E. & Bartlett, S.R. (2007). Role of atypical protein kinase C isozymes and NF-B in IL-1-induced expression of cyclooxygenase-2 in human myometrial smooth muscle cells. J. Cell. Physiol. 210:637-643

Siow, R.C.M., Ishii, T. & Mann, G.E. (2007). Modulation of antioxidant gene expression by 4-hydroxynonenal: atheroprotective role of the Nrf2/ARE transcription pathway. Redox Report 12:11-15

Mann, G.E., Niehueser-Saran, J., Watson, A., Gao, L., Ishii, T., de Winter, P. & Siow, R.C.M. (2007). Nrf2/ARE regulated antioxidant gene expression in endothelial and smooth muscle cells in oxidative stress: implications for atherosclerosis and pre-eclampsia. Acta Physiol. Sinica 59:117-127

Siow, R.C.M., Li, F.Y.I., Rowlands, D.J., de Winter, P. & Mann, G.E. (2007). Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. Free Radic. Biol. Med. 42:909-925

Afzal-Ahmed, I., Mann, G.E., Shennan, A. Poston, L. & Naftalin, R.J. (2007) Pre-eclampsia inactivates glucose-6-phosphate dehydrogenase and impairs the redox status of erythrocytes and fetal endothelial cells. Free Radic. Biol. Med. 42: 1781-1790

Mann, G.E., Rowlands, D.J., Li, F.Y.I., de Winter, P. & Siow, R.C.M. (2007). Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc. Res. 75:261-274

de Meirelles, L.R., Mendes-Ribeiro, A.C., Santoro, M.M., Mendes, M.A.P., da Silva, M.N.S.B., Mann, G.E., Brunini, T.C. (2007). Inhibitory effects of endogenous L-arginine analogues on nitric oxide synthesis in platelets: role in platelet hyperaggregability in hypertension. Clin. Exp. Pharmacol. Physiol. 34:1267-1271

de Sa, S.M., Martins, M.A., Rodrigues, P.N., Bandeira, M.M., Santos, S.F., Mann, G.E., Mendes-Ribeiro, A.C. & Brunini, T.M. (2007). Modulation of the cationic amino acid transport system y+L by surface potential, ouabain and thrombin in human platelets: effects of uremia. Nephron Exp. Nephrol. 107:e132-e138

Brunini, T.M.C., Roberts, N., Yaqoob, M., Ellory, J., Mann, G.E., & Ribeiro, A.C.M. (2006). Activation of L-arginine transport in undialysed chronic renal failure and continuous ambulatory peritoneal dialysis patients. Clin. Exp. Pharmacol. Physiol. 33:114-118.

Brunini, T.M.C., Yaqoob, M.M., Roberts N.B., Ellory, J.C., Moss, M.B., Siqueira, M.A.S., Mann, G.E., Mendes-Ribeiro, A.C. (2006). Characterisation of cationic amino acid transport systems in rat erythrocytes: Lack of effect of uraemia on L-arginine influx. Clin. Exp. Pharmacol. Physiol. 33:702-707

Douglas, G., Armitage, J.A., Taylor, P.D., Lawson, J.R., Mann, G.E. & Poston, L. (2006). Cardiovascular consequences of life long exposure to dietary isoflavones in the rat. J. Physiol. 571.2:477-487

Borrás, C., Gambini, J., Carmen Gómez-Cabrera, M., Sastre, J., Pallardó, F.V., Mann, G.E. & Viña, J. (2006). Genistein, a soy isoflavone, upregulates the expression of antioxidant genes via the estrogen receptors-MAPK-NFB pathway. FASEB J. 20:E1-E6

Knock, G.A., Mahn. K., Mann. G.E., Ward, J.P. & Aaronson, P.I. (2006). Dietary soy modulates endothelium-dependent relaxation in aged male rats: increased agonist-induced endothelium-derived hyperpolarising factor and basal NO activity. Free Radic. Biol. Med. 41:731-730

Joy, S., Siow, R.C.M., Rowlands, D.J., Wyatt, A.W., Coen, C.W., Jacob, R., Kallo, I. & Mann, G.E. (2006). The isoflavone equol mediates rapid vascular relaxation: Ca2+-independent activation of eNOS/Hsp90 involving ERK1/2 and Akt phosphorylation in human endothelial cells. J. Biol. Chem. 281:27335-27345

Harris, L., Mann, G.E. & Leake, D.S. (2006). Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein. Arch. Biochem. Biophys. 455:68-76

Queen, L.R., Ji, Y., Young, L., Yao, K., Wyatt, A.W., Rowlands, D.J., Siow, R.C.M., Mann, G.E. & Ferro, A. (2006). Mechanisms underlying 2-adrenoceptor mediated nitric oxide generation by human umbilical vein endothelial cells. J. Physiol. 576.2:585-594

Reis, P.F., da Silva, C.D., Brunini, T.M., Moss, M.B., Siqueira, M.A., Santos, S.F., Roberts, N.B., Ellory, J.C., Mann, G.E. & Mendes-Ribeiro, A.C. (2006). Plasma amino acid profile and L-arginine uptake in red blood cells from malnourished uremic patients. J. Renal Nutr. 16:325-331

Ashman, N., Brunini, T.M., Mann, G.E., Mendes-Ribeiro, A.C., Yaqoob, M.M. (2006). Increased L-arginine transport via system b0,+ in human proximal tubular cells exposed to albumin. Clin. Sci. (London) 111:389-399

da Silva, D.C., Brunini, T.M.C., Reis, P.F., Moss, M.B., Santos, S.S., Roberts, N.B., Ellory, J.C., Mann, G.E. & Mendes-Ribeiro, A.C. (2005). Effects of nutritional status on the L-arginine-nitric oxide pathway in platelets from hemodialysis patients. Kidney Intern. 68:2173-2179.

Anwar, A., Li, F-Y, Leake, D.S., Mann, G.E. & Siow, R.C.M. (2005). Nrf2-mediated induction of heme oxygenase-1 by oxidised LDL in human vascular smooth muscle cells: role of mitogen-activated protein kinases. Free Radic. Biol. Med. 39:227-236.

Mahn, K., Borrás, C., Knock, G.A., Taylor, P., Khan, I.Y., Sugden, D., Poston, L., Ward, J.P.W., Sharpe, R.M., Viña, J., Aaronson, P.I. & Mann, G.E. (2005). Dietary soy protein increases antioxidant and eNOS gene expression leading to improved endothelial function and reduced blood pressure in vivo. FASEB J. 19:1755-1757

Borrás, C., Gambini, J, Carmen Gómez-Cabrera, M-A., Sastre, J., Pallardó, F.V., Mann, G.E. & Viña, J. (2005). 17B-oestradiol upregulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2 MAPK/NFB cascade. Aging Cell 4:113-118.