BIO 2009 – Atlanta, 18–21 May, 2009 BIO Europe Spring 2009 – Milano, 16-18 March 2009 BIO 2008 – San Diego, 17-20 June 2008 BIO 2007 - Boston, 6-9 May 2007 (Booth 2025) BIO Europe Spring 2007 - Milano, 5-7 March 2007 BIO 2006 - Chicago, 9-12 April 2006 EMBO 2006 - Milano, 8-11 February 2006 (Bio3 Research sponsor) BIO 2005 - Philadelphia, 19-22 June 2005 Cytokines & Inflammation - San Francisco, 27-28 January 2005 BioData 2005 - Geneva 25-26 January 2005 BIO Europe - Cologne , 8-10 November 2004 BIO 2004 - San Francisco, 6-9 June 2004 BIO 2002 - Toronto, 8-12 June 2002
Posters Abstract's presented at Cytokines and Inflammation conference:
Abstract Title: SMOOTH MUSCLE CELLS IN HUMAN ATHEROSCLEROTIC PLAQUES SECRETE AND RESPOND TO HMGB1
Authors & Affiliation: Annalisa Porto, Roberta Palumbo, Maurizio Pieroni, Gianfranco Appigliano, Roberto Chiesa, Francesca Sanvito, Attilio Maseri, and Marco E. Bianchi
Molecular Biology and Functional Genomics (A.P.), Cardio-Thoracic and Vascular (M.P., G.A., R.C.), Pathology (F.S.) Departments, San Raffaele Scientific Institute, via Olgettina 60, 20132 Milan, Italy; Institute of Cardiology, Catholic University, largo A. Gemelli 8, 00168 Rome, Italy (A.P.); and San Raffaele University, via Olgettina 58, 20132 Milan, Italy (R.P., A.M., M.E.B.)
Presenting Author/Contact information (please include Telephone and email):
Francesco Paolo Pilato Bio3 Research Srl, Via della Moscova, 6/8 - 20121 Milano (Italy) Telephone number: +39-02-62694888 email: f.pilato@bio3research.com
Abstract: High Mobility Group Protein 1 (HMGB1) is a chromatin protein leaked out by necrotic cells and secreted by activated myeloid cells. The extracellular protein is a potent mediator of inflammation and may represent a relevant therapeutic target. We tested whether cells within human atherosclerotic plaques could secrete HMGB1 and respond to it.
We put into culture human carotid endoarterectomy specimens (n=25), obtained from patients with >70% carotid stenosis, and normal internal mammary arteries specimens from patients (n=10) undergoing coronary artery by-pass surgery. We found HMGB1 in the supernatant of atherosclerotic but not of normal arteries. Secreted HMGB1 originated from cytoplasmic HMGB1 expressed by endothelial, neointimal foam cells and also by smooth muscle cells (SMCs) within atherosclerotic plaques but not in normal arteries. After cholesterol loading HMGB1 was secreted by cultured SMCs isolated from normal and atherosclerotic arteries. In turn in response to HMGB1, SMCs proliferate, migrate and secrete HMGB1 themselves.
Thus, SMCs are both a source and a target of HMGB1 in atherosclerotic disease. Currently available HMGB1 blockers might be used in the local treatment of atherosclerotic disease and in-stent restenosis. Development of direct/indirect inhibitors is ongoing, as described in the poster by S.Fumero.
Abstract Title: A NEW FEATURE OF K-252a: INHIBITION OF HMGB1-INDUCED CELL PROLIFERATION AND MIGRATION
Authors & Affiliation: Fumero S.*, Barone D.*, Bertarione Rava Rossa L.*, Pilato F.P.**, Bianchi M. E. #, Bucci E.
* Creabilis Therapeutics SpA, Via Ribes, 5 10010 - Colleretto Giacosa (TO) - Italy ** Bio3 Research Srl, Via Manzoni, 46 - 20121 Milano (Italy) # Istituto Scientifico San Raffaele, Via Olgettina, 58 - 20132 Milano (Italy) Istituto di Biostrutture e Bioimmagini CNR, Via Mezzocannone, 16 - 80134 Napoli (Italy)
Presenting Author/Contact information (please include Telephone and email):
Abstract: K-252a, an indolo-carbazole originally derived from Nocardiopsis sp., is a very well known inhibitor of TrkA, TrkB, TrkC, pkA, pkC, pkG, CaM kinase, MLC kinase, phosphorylase kinase, MAP kinase and numerous other kinases by acting as a competitive inhibitor with respect to ATP.
K-252a is under development for topical treatment of psoriasis by Creabilis Therapeutics, as inhibitor of NGF-receptor TrkA. K-252a was tested in in vitro models of cell proliferation and migration induced by HMGB1.
K-252a inhibited both activities at 30-100 nM range. On the contrary, cell migration induced by fMLP was not inhibited by K-252a. Since HMGB1 is secreted by smooth muscle cells in human atherosclerotic plaques (Porto et al, this conference), it is conceivable to consider K-252a and its derivatives as potential therapeutic agents against HMGB1 in restenosis through systemic administration or through drug-eluting stents. Since circular dichroism showed that K-252a does not have direct effect on HMGB1, it is reasonable to think that K-252a acts through one or more kinases of the pathway activated by HMGB1. Studies are ongoing to identify which kinases are involved.
Bio3 News...
Bio3 Research S.r.l. (Milano – Italy), is pleased to announce the official
opening of a Californian subsidiary, located in Hayward…
