Cambridge, England, September 11-14, 2011


Scientific Program


Sunday, 11. September 2011


Evening Session


15:0017:00 Registration and Check-In
Clare College, University of Cambridge

17:00
19:00 Welcome Reception
Scholars' Garden, Old Court, Clare College, University of Cambridge

19:0020:00 Opening Ceremony
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge

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Chairs:
Matthias Barton
University of Zurich, Switzerland
Anthony P. Davenport
University of Cambridge, United Kingdom


19:00 – 19:15
Conference Chairs' Welcome Address

19:15 – 20:00 Key Note Lecture



The History of Endothelium-Dependent Contraction
Paul M. Vanhoutte
University of Hong Kong, SAR, China



Monday, 12. September 2011


Morning Session


08:3009:15 Plenary Session
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Martine Clozel
Actelion Pharmaceuticals Ltd., Switzerland
Duncan J. Stewart
University of Ottawa, Canada

08:30 – 09:15 Plenary Lecture



Evolution and Current State of Endothelin Receptor Antagonism in Pulmonary Hypertension
Lewis J. Rubin
University of California San Diego, United States of America

09:1510:15 Symposium I: Pharmacology of Endothelin Receptors and Antagonists
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Janet J. Maguire
University of Cambridge, United Kingdom
Jo G.R. de Mey
University of Maastricht, The Netherlands


09:15 – 09:30
A Novel Endothelin Receptor Antagonist Increases Rates of Cerebral Malaria Survival
Minxian Dai, Henry J. Shikani, Ralph A. Stephani*, Sandra E. Reznik, Herbert B. Tanowitz, Louis M. Weiss, Mahalia S. Desruisseaux

09:30 – 09:45 Mouse mucosal mast cell protease 4 generates endothelin-1 in vitro and in vivo
Martin Houde*, Julie Labonté, Marc-David Jamain, Gunnar Pejler, Michael Gurish, Shinji Takai, Pedro D'Orléans-Juste

09:45 – 10:00 Endothelin converting enzyme-1 genetic inhibition prevents bleomycin-induced pulmonary fibrosis in mice.
Anggoro B. Hartopo*, Nur Arfian, Dwi A.A. Nugrahaningsih, Nicolas Vignon-Zellweger, Susi Heiden, Kazuhiko Nakayama, Keiko Yagi, Ken-ichi Hirata, Noriaki Emoto

10:00 – 10:15 Arterial anti-endothelinergic effects of calcitonin gene-related peptide in vitro and in vivo.
Merlijn Meens*, Jelly Nelissen, Matthijs Compeer, Paul Schiffers, Ben Janssen, Jo G. R. De Mey


10:15 – 10:45
Coffee Break


10:45 – 11:45 Symposium II: Endocrinology and Reproductive System
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Yasuo Matsumura
Osaka University of Pharmaceutical Sciences, Japan
Sidney G. Shaw
University of Bern, Switzerland


10:45 – 11:00
Involvement of endothelin system in polycystic ovarian syndrome.
Rina Meidan*, Arye Hurwitz, Ronit Haimov-Kochman, Eyal Klipper, Tal Imbar

11:00 – 11:15 Involvement of endothelin B receptors in the increase of plasma glucose and NEFA with a GH-independent manner in cattle.
Hongqiong Zhao*, Sint ThanThan, Swe Yannaing, Hideto Kuwayama

11:15 – 11:30 Endothelin-2 induce ovulation by constricting ovarian follicle via EDNRA-mediated pathway.
Jongki Cho*, Masashi Yanagisawa, Chemyong Ko

11:30 – 11:45 Opposing roles of endothelin receptors in regulating ovulation and luteal function. 
CheMyong Ko*, Jongki Cho, Heyyong Kim, Masashi Yanagisawa, Po-Ching Lin  



11:45
12:15 ET-12 Conference Group Photograph
In front of King's College next to Clare College Old Court



Afternoon Session

12:1514:00 Posters Session I: Cardiovascular and Myocardial Physiology and Disease; Pharmacology of Endothelin Receptors and Antagonists; Results from New Clinical Studies
Elton-Bowring Room, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge

Moderators of Poster Session I:



Janet J. Maguire
University of Cambridge, United Kingdom
Jo G.R. de Mey
University of Maastricht, The Netherlands
Yasuo Matsumura
Osaka University, Japan




Dennis L. Andress
Abbott Laboratories, United States of America
Noriaki Emoto
Kobe University, Japan
Sidney G. Shaw
University of Bern, Switzerland

14:0015:30 Symposium III: Cardiovascular and Myocardial Physiology and Disease
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Adviye Ergul
Georgia Health Sciences University, United States of America
Pedro d’Orléans Juste
University of Sherbrooke, Canada


14:00 – 14:30 Invited Lecture



Endothelin in Vascular Disease and Insulin Resistance
John Pernow
Karolinska Institutet, Stockholm, Sweden

14:30 – 14:45 Anti-TNF-α therapy ameliorates cardiac function in mice with reduced endogenous endothelin-1 and increased afterload.
Susi Heiden*, Nicolas Vignon-Zellweger, Shigeru Masuda, Keiko Yagi, Kazuhiko Nakayama, Masashi Yanagisawa, Noriaki Emoto

14:45 – 15:00 The adipokine chemerin increases vascular reactivity to ET-1 via activation of ERK1/2.
Karla Neves*, Núbia Lobato, Fernando Filgueira, Ana Maria Oliveira, Rita Tostes

15:00 – 15:15 Modulation of release of Endothelin-1 in hypertrophic human endocardial and vascular endothelial cells.
Johny Al-Khoury*, Dima Abdel Samad, Chantale Provost, Sheldon Magder, Pedro D'Orléans-Juste, Ghassan Bkaily, Danielle Jacques

15:15 – 15:30 Systemic endothelin receptor blockade in acute ST-segment elevation acute coronary syndrome protects the microvasculature - a pilot study
Christopher Adlbrecht*, Martin Andreas, Bassam Redwan, Klaus Distelmaier, Julia Mascherbauer, Gilbert Beran, Alexandra Kaider, Michael Wolzt, Ioana-Alexandra Tilea, Thomas Neunteufl, Georg Dell-Karth, Gerhard Kreiner, Gerals Maurer, Irene M. Lang.

15:30 – 15:45 Endothelial overexpression of endothelin-1 augments endothelium-dependent contractions in the mouse carotid artery.
Oliver Baretella*, François YL Li, Eva HC Tang, Aimin Xu, Sookja K. Chung, Paul M. Vanhoutte


15:45 – 16:15 Coffee Break


16:15
17:15 Symposium IV: General Physiology, Development, and Aging
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Noriaki Emoto
Kobe University, Japan
Subrata Chakrabarti
University of Western Ontario, Canada


16:15 – 16:30 Endothelin receptor A antagonism prevents fetal growth restriction in pregnant eNOS-/- mice.
Kehuan Luo, Larry G Thaete*, Xiao-Wu Qu, Mark G Neerhof

16:30 – 16:45 Increased vasoactive factors and extracellular matrix proteins in the retina and heart in type 2 diabetes are prevented by macitentan, a dual endothelin receptor antagonist.
Subhrojit Sen*, Shali Chen, Biao Feng, Marc Iglarz, Subrata Chakrabarti

16:45 – 17:00 Signalling Requirements for ET-1-Induced Hypertrophy.
Caroline R. Archer*, Martin D. Bootman, H. Llewelyn Roderick

17:00 – 17:15 Dendritic cell regulation of endothelin-1 by endogenous Toll-like receptor ligands: implications for autoimmune disease
Hemanshu Patel*, Rolf Spirig, Robert Rieben, Janice Tsui, Sidney Shaw.


18:00 Young Investigators Event
Junior Common Room, Old Court, Clare College, University of Cambridge


Tuesday, 13. September 2011


Morning Session


08:3010:00 Symposium V: Renal, Fluid and Electrolyte Physiolology and Renal Disease
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Ariela Benigni
Mario Negri Institute, Bergamo, Italy
Pierre-Louis Tharaux
University of Paris, France


08:30 – 09:00 Invited Lecture



Let's Talk Sex: Endothelin and Control of Sodium Excretion
David M. Pollock
Georgia Health Sciences University, Augusta, United States of America


09:00 – 09:15 Identification of the site of endothelin A receptor antagonist-induced fluid retention.
Donald Kohan*, Kevin Strait, Peter Stricklett, Mark Chapman, Deborah Stuart

09:15 – 09:30 Chronic endothelin-1 infusion in rats increases glomerular permeability to albumin and proximal tubular albumin uptake as determined by intravital microscopy.
David Pollock*, Mohamed Saleh, Ruben Sandoval, George Rhodes, Silvia Campos, Bruce Molitoris

09:30 – 09:45 The ET-1 / Endothelin A receptor axis for the integrity of the glomerular filtration barrier under diabetes in mice.
Nicolas Vignon-Zellweger*, Bambang Widyantoro, Susi Heiden, Kazuhiko Nakayama, Keiko Yagi, Masashi Yanagisawa, Noriaki Emoto

09:45 – 10:00 Endothelial Cell derived Endothelin-1 Knockdown Attenuates Kidney Fibrosis via Reducing Peritubular Capillary Loss and Pericyte to Myofibroblast Transition.
Nur Arfian*, Dwi Aris A. Nugrahaningsih, Anggoro B. Hartopo, Nicholas V. Zellweger, Susi Heiden, Kazuhiko Nakayama, Keiko Yagi, Masashi Yanagisawa, Ken-ichi Hirata, Noriaki Emoto


10:00 – 10:30 Coffee Break

10:30-12:00 Symposium VI: Immunology, Inflammation, and Cancer
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge






Chairs:
Anna Bagnato
Istituto Nazionale Tumori Regina Elena, Rome, Italy
Anil Gulati
Midwestern University, United States of America


10:30 – 11:00 Invited Lecture



New Role for Endothelin Receptors in Tumor Metastasis: Implications for Cancer Therapy
Dan Theodorescu
University of Colorado at Denver, United States of America

11:00 – 11:15 Deciphering the transcriptional complex critical for epigenetic regulation driven by endothelin A receptor/β-arrestin-1 in ovarian cancer.
Laura Rosano*, Roberta Cianfrocca, Piera Tocci, Francesca Spinella, Valeriana Di Castro, Erica Salvati, Annamaria Biroccio, Pier Giorgio Natali, Anna Bagnato

11:15 – 11:30 Dissecting the complex crosstalk network between endothelin-1 axis and vascular endothelial growth factor system in melanoma cells.
Francesca Spinella*, Valentina Caprara, Laura Rosanò, Valeriana Di Castro, Roberta Cianfrocca, Pier Giorgio Natali, Anna Bagnato

11:30 – 11:45 Endothelin-1 stimulated gene induction within colon cancer cells and fibroblasts and the effect of endothelin receptor antagonism on key genes.
Samer-ul Haque*, Hazel Welch, Michael Dashwood, Xu Shiwen, David Abraham, Mo Heetun, Noreen Farooqui, Irving Taylor, Marc Winslet, Marilena Loizidou

11:45 – 12:00 Molecular mechanisms regulating ECE-1 expression in prostate cancer.
Alison Whyteside*, Anthony Turner, Daniel Lambert


Afternoon Session

12:0014:00 Posters Session II: General Physiology, Development, and Aging; Renal, Fluid and Electrolyte Physiology and Renal Disease; Immunology, Inflammation, and Cancer
Elton-Bowring Room, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge

Moderators of Poster Session II:



Adviye Ergul
Georgia Health Sciences University, United States of America
Pierre-Louis Tharaux
University of Paris, France
Ariela Benigni
Mario Negri Institute, Bergamo, Italy



Joey P. Granger
University of Mississippi Medical Center, United States of America
Anil Gulati
Midwestern University, United States of America
Markus P. Schneider
University of Glasgow, United Kingdom


14:0014:30 Symposium VII: Clinical Trials Update 2011
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge




Chairs:
David Langleben
McGill University, Canada
John Pernow
Karolinska Institutet, Stockholm, Sweden


14:00 – 14:30 Invited Lecture



Challenges in the Clinical Application of Endothelin Antagonists
David J. Webb
University of Edinburgh, United Kingdom

Clinical Trial Updates

14:30 – 14:45 Atrasentan for diabetic nephropathy
Dennis Andress, Abbott Laboratories, United States of America

14:45 – 15:00 Scientific basis and description of Actelion's trials with ERAs. The next frontiers
Martin Clozel, Actelion Ltd., Switzerland

15:00 – 15:15 Anbrisentan: Key preclinical and clinical study updates
Hunter C. Gillies, Gilead/GlaxoSmithKline, United States of America

15:15 – 15:30 ET receptors and receptor antagonists: lessons learned, future directions
Neil Davie, Pfizer, United States of America


15:30 – 16:00 Coffee Break

16:0017:45 Special Session VIII: Clinical trials with ERAs: What went wrong and where can we improve?
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge


Moderator:
Donald E. Kohan
University of Utah, United States of America

Panelists:



John G. Cleland
University of Hull, United Kingdom
Panelist, ERA Trials in Heart Failure

Lewis J. Rubin
University of California San Diego, United States of America
Panelist, ERA Trials in Pulmonary Disease




Dan Theodorescu
University of Colorado at Denver, United States of America
Panelist, ERA Trials in Cancer

Donald E. Kohan
University of Utah, Salt Lake City, United States of America
Panelist, ERA Trials in Renal Disease


17:4518:00 ET-12 Awards Ceremony
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge




Chairs:
Matthias Barton
University of Zurich, Switzerland
Anthony P. Davenport
University of Cambridge, United Kingdom


19:00 Pre-Banquet Reception
Scholars' Garden, Old Court, Clare College, University of Cambridge

19:30 Conference Banquet
Great Hall, Old Court, Clare College, University of Cambridge



Wednesday, 14. September 2011


Morning Session


08:3010:00 Symposium IX: Cell Biology and Tissue-Specific Roles of Endothelin and its Receptors
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge




Chairs:
Takashi Miyauchi
University of Tsukuba, Japan
Hunter C. Gillies
Gilead Sciences, Inc., United States of America


08:30 – 09:00 Invited Lecture


Genetics and epigenetics of the endothelin gene
Brian D. Cain
University of Florida at Gainesville, United States of America


09:00 – 09:15 ET-1 modulates tubular and reticular structures in the nucleus.
Levon Avedanian*, Danielle Jacques, Pedro D'Orleans-Juste, Ghassan Bkaily

09:15 – 09:30 Endothelin (ET)-1, via ETA receptor, activates ß-arrestin-mediated signaling pathways and promotes podocyte migration in vitro: possible implications for proliferative lesions in chronic kidney disease.
Simona Buelli*, Elena Gagliardini, Laura Rosanò, Anna Pezzotta, Laura Bagnato, Giuseppe Remuzzi, Ariela Benigni

09:30 – 09:45 Knockdown of bone morphogenic protein receptor–II by siRNA increases in vitro endothelin-1 synthesis by human pulmonary microvascular endothelial cells.
Gregory Star*, Michele Giovinazzo, David Langleben

09:45 – 10:00 Protein kinase C α regulates nuclear pri-microRNA 15a release as part of endothelin signaling
Melanie von Brandenstein*, Reinhard Depping, Ekaterine Schäfer, H.-P. Dienes, Jochen W. U. Fries

10:00 – 10:30 Coffee Break


10:30 – 12:00 Symposium X: Results from New Clinical Studies
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge






Joey P. Granger
University of Mississippi Medical Center, United States of America
Neil J. Davie
Pfizer Inc., United Kingdom


10:30 – 10:45
The endothelin receptor antagonist bosentan improves peripheral endothelial function in patients with type 2 diabetes mellitus and microvascular complications.
Arnar Rafnsson*, Felix Böhm, Magnus Settergren, Adrian Gonon, Kerstin Brismar, John Pernow

10:45 – 11:00 A Phase I, open label, ascending dose study of the safety, tolerability, pharmacokinetics and pharmacodynamics of the endothelin B agonist, SPI-1620, in patients with recurrent or progressive carcinoma.
Anthony Tolcher*, Venkat Gari, Guru Reddy, Luigi Lenaz, George Tidmarsh, Anil Gulati

11:00 – 11:15 Ameliorating day- and night-time blood pressure control by combined ECE/NEP inhibitor on top of losartan: a randomized, cross-over, placebo-controlled clinical trial in patients with type 2 diabetes and albuminuria.
Irene van der Meer, Ariela Benigni*, Aneliya Parvanova, Ilian Iliev, Sanjib Sharma, Jose Cruz, Giuseppe Remuzzi, Piero Ruggenenti

11:15 – 11:30 Endothelin/endothelin receptor system is upregulated in preeclampsia with or without fetal growth restriction in contrast to gestational diabetes.
Martina Dieber-Rotheneder, Melanie Fellner, Sanja Beganovic, Gernot Desoye, Mila Cervar-Zivkovic*


11:30 – 11:45 Chronic endothelin A receptor antagonism modifies novel cardiovascular risk factors in chronic kidney disease
Neeraj Dhaun, Scott Haugie, Jane Goddard, David J. Webb


Afternoon Session

11:4514:00 Poster Session III: Neurophysiology, Neurobiology, Stroke, and Pain; Endocrinology and Reproductive System; Cell Biology and Tissue-Specific Roles of Endothelin and its Receptors
Elton-Bowring Room, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge

Moderators of Poster Session III:



Giles A. Rae
University Federal de Santa Caterina, Brazil
Michael R. Dashwood
University College London, United Kingdom
Neil J. Davie
Pfizer Inc., United Kingdom



Subrata Chakrabarti
University of Western Ontario, Canada
Takashi Miyauchi
University of Tsukuba, Japan
Hunter C. Gillies
Gilead Sciences, Inc., United States of America


2:00
3:30 Symposium XI: Neurophysiology, Neurobiology, Stroke, and Pain
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Michael R. Dashwood
University College London, United Kingdom
Giles A. Rae
Universidade Federal de Santa Caterina, Brazil

14:00 – 14:15 ETB receptor agonist, IRL-1620 prevents beta amyloid (Aβ) induced cognitive impairment in normal and diabetic rats.
Anil Gulati*, Seema Briyal, Cortney Shepard

14:15 – 14:30 Increased Endothelin B Receptor Expression Contributes to Retinal Ganglion Cell Death in a Rodent Model of Glaucoma.
Raghu Krishnamoorthy*, Alena Minton, Hai-Ying Ma, Nitasha Phatak, Shaoqing He, Dorota Stankowska, Ming Jiang, Brett Mueller

14:30 – 15:45 Relevance of endothelin-1(1-31) synthesis in hind paw nociception mediated by activation of mast cells in mice.
Amelia Somensi, Pedro D'Orleans-Juste, Giles Rae*

14:45 – 15:00 Opposite interactions between endothelin-1 sensitization and post-incisional pain in the rat hindpaw.
Tyrrell Jenkins, Alla Khodorova, Jeffrey Wang, Gary R. Strichartz* 


15:00 – 15:30 Coffee Break



15:3016:20 Endothelin: Quo vadis in 2011?
Riley Auditorium, The Gillespie Centre, Memorial Court, Clare College, University of Cambridge





Chairs:
Matthias Barton
University of Zurich, Switzerland
Anthony P. Davenport
University of Cambridge, United Kingdom


15:30 – 16:00 Special Lecture



Highlights of ET-12
Masashi Yanagisawa
University of Texas Southwestern, Dallas, United States of America

16:0016:10 Announcement of ET-12 Best Oral and Poster Presentation Award Winners
Masashi Yanagisawa
University of Texas Southwestern, Dallas, United States of America

16:10 – 16:20 Closing Remarks by the Conference Chairs