NEWSLETTER of the FONDATION LEDUCQ Improving health through international

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NEWSLETTER of the FONDATION LEDUCQ Improving health through international Powered By Docstoc
                  Improving health through international cardiovascular research            !
                                                                           Winter 2008
An Anchor Gone                 2    Interest in Transatlantic Network
                                      Grants Reaches Record Level
Investigators from the
cycAMP Network show how
an A-Kinase Anchoring Protein
can cause cardiac hypertrophy

New Transatlantic               3
Fellows Named
The 2008-9 Leducq
Transatlantic Fellowships
were awarded in October

Scientific Advisory 4
Committee Welcomes
New Members
                                    Fondation Leducq received a record high of
Drs. Michel Lazdunski, Joseph
Loscalzo and Richard Weisel         79 expressions of interest for the 2008-9
join the Scientific Advisory        Transatlantic Network grant application
                                    cycle. This is more than double the number
                                    received last year, and is the result of a
Network Focus!!!!!!!!!!!!!!!!!!!5
                                    concerted effort to increase awareness of the
Insight into the cause of
peripartum cardiomyopathy           grants.
from a Fondation Leducq               In the spring, letters describing the Transatlantic
Transatlantic Network
                                    Network program were sent to more than 400 academic
                                    medical institutions in North America and Europe.
 Volume 1, Number 1                                                                          Winter 2008

                                                                                          Number of
 Traffic on the Fondation website subsequently
 increased in the months leading up to the                      Research Area             of Interest
 September application deadline. As a result, this                                         Received
 year's proposals were remarkable for their range of                                        in 2008
 topics and participating institutions (see Table).    Coronary disease, vascular
                                                       biology, thrombosis
    Up to 4 Transatlantic Network grants are
 awarded each year. Providing $6 million over 5        Heart failure, myocardial
 years for each Network, the grants are intended to    function
 foster collaborative research efforts between North   Stem cells, regeneration                 6
 American and European teams.
                                                       Stroke                                   6
    Selection of the Networks is a two-stage
 process. In October, the Scientific Advisory          Obesity, metabolic syndrome              6
 Committee reviews the expressions of interest and     Arrhythmias                              5
 selects those that proceed to a full application.     Congenital heart disease                 5
 Full applications are then reviewed and grant
                                                       Epidemiology                             4
 recipients selected at the committee's April
 meeting. This year, only 12 out of the 79             Imaging, computer modeling               4
 proposals were selected to submit a full              Hypertension, renal disease              3
                                                       Valve disease                            2
 Check our Spring issue for 2008-9 Network grant
 winners!                                              Other                                    1

 An Anchor Gone Astray
    Chronic stress on the           team led by Dr. John D.            blunted the hypertrophy.
 heart, from conditions like        Scott demonstrated that A-         Finally, increased AKAP-Lbc
 high blood pressure,               Kinase Anchoring Protein           levels were also found in
 diseased heart valves, and         (AKAP)-Lbc is key to the           patients with hypertrophy.
 high levels of catecholamine       development of hypertrophy.           The team is now creating
 hormones like adrenaline,             Anchoring proteins keep         transgenic mice to test
 can lead to hypertrophy, or        enzymes in specific locations      whether AKAP-Lbc over-
 increase in the size, of           to accelerate biochemical          expression is sufficient to
 cardiac muscle cells. While        reactions inside a cell. AKAP-     cause hypertrophy and
 initially adaptive, cardiac        Lbc levels were increased in       whether AKAP-Lbc
 hypertrophy, which affects         hypertrophic cardiac cells of      inactivation protects against
 14 to 18% of adults,               rats exposed to catechol-          its development.
 eventually becomes harmful.        amines. AKAP-Lbc promoted             Dr. Scott is the American
    In research supported by        the expression of genes            coordinator of the Localized
 the Fondation Leducq and           linked to hypertrophy,             !"#$%"&'"(')*+,'-./#0&.#/'0#1'
 reported in the October 24th       whereas silencing of AKAP-         2"34&'564%07.48'("%'940%$':0.&;%4!
 issue of Molecular Cell, a         Lbc by RNA interference            5%0#80$&0#$.)'24$<"%=>'

 Volume 1, Number 1                                                                            Winter 2008

                                                       The Leducq Transatlantic
 New Transatlantic Fellows Named
                                                       Fellowship Program was
 started in 2007 to promote the development of young researchers committed
 to international collaborations in cardiovascular disease research. Fellows
 spend 2 years working in an established Leducq Transatlantic Network,
 including at least 1 year on the opposite side of the Atlantic from their
 country of origin. The 2008-9 Fellowships have been awarded to Matti
 Junttila, MD, DMSc, and Astrid van Hylckama Vlieg, PhD.

                                  Dr. Junttila is           Dr. van
                              currently a cardiology     Hylckama Vlieg, a
                              fellow at the University   clinical
                              of Oulu, Finland. He       epidemiologist, is a
                              will work for 2 years      post-doctoral fellow
                              with Dr. Richard           in Leiden, the
                              Myerburg at the            Netherlands. She
                              University of Miami, in    currently works
                              the Preventing Sudden      with Dr. Frits
                              Death Network.             Rosendaal in the
     Dr. Junttila, who has previously studied            Leducq International Network Against
 abnormal cardiac rhythms such as atrial fibrillation    Thrombosis. She will join Network member Dr.
 and Brugada syndrome, will focus on sudden              Bruce Psaty at the University of Washington in
 cardiac death (SCD), which accounts for more            Seattle for 1 year before returning to Leiden.
 than half of all cardiovascular deaths. Because            Dr. van Hylckama Vlieg has long been
 SCD may be the first manifestation of previously        interested in identifying the risk factors for
 silent cardiac disease, the Network aims to             venous thrombosis, or clots in the veins. The
 improve the identification of individuals at risk for   hormones present in oral contraceptive pills and
 SCD. The central hypothesis of Dr. Junttila’s           hormone replacement therapy, used by over 100
 project is that SCD risk has a genetic basis. To        million women worldwide, are known to
 discover genetic variants associated with increased     increase venous thrombosis risk. Dr. van
 vulnerability to SCD, he will compare the DNA           Hylckama Vlieg will analyze how other
 sequences of 2 high-risk patient populations,           medications, such as cholesterol-lowering statins,
 victims of SCD and patients whose cardiac rhythm        and genetic factors modify the thrombosis risk
 is altered by certain medications, with those of        associated with hormonal therapy. Since
 unaffected individuals. Finding genetic variations      hormonal therapy is used so commonly, even a
 unique to the affected patients will advance our        small change in thrombosis risk may have a large
 understanding of the molecular mechanisms               epidemiological impact.
 underlying SCD and how to prevent it.

 Volume 1, Number 1                                                                     Winter 2008

 Scientific Advisory Committee Welcomes
 New Members
 The October Scientific Advisory      journal of the American Heart
 Committee meeting in New York        Association.
 marked the arrival of 3 new             Dr. Loscalzo's research focuses
 members, Michel Lazdunski,           on the molecular processes in
 PhD, Joseph Loscalzo, MD,            blood vessels that lead to
 PhD, and Richard Weisel, MD.         atherosclerosis (inflammation and
    Dr. Lazdunski is the director     cholesterol build-up in the artery
 of the Centre National de la         wall) and thrombosis (blood clots
 Recherche Scientifique (CNRS)        that can cause heart attacks). In     "#$!%&'()*!+,-./012&!
 Institute of Molecular and Cell      particular, his work focuses on
 Pharmacology as well as Chair of     nitric oxide, a key messenger
 Molecular Pharmacology at the        produced by the endothelial cells
 University of Nice. Among his        that line the inside of blood
 many distinctions, Dr. Lazdunski     vessels.
 won the CNRS Gold Medal in              Dr. Weisel is Chair of Cardiac
 2000 for his research on ion         Surgery at the University of
 channels.                            Toronto and Director of the
    Ion channels are proteins that    Toronto General Research
 enable the movement of sodium,       Institute.
 potassium and calcium into and          In addition to developing
 out of cells. Dr. Lazdunski's        techniques to protect the heart
 discoveries have offered insight     from injury during cardiac surgery,   "#$!341)5(!+41',*-4!
 into the mechanisms underlying       Dr. Weisel investigates different
 processes like pain perception,      strategies for restoring heart
 seizures, and cardiac arrhythmias,   function after heart attacks. These
 and have revealed how various        strategies include transplantation
 drugs work, including anesthetic     of heart cells and bone marrow
 gases, calcium-channel blockers      stem cells, genetically enhanced
 for high blood pressure, and         cells, and tissues engineered using
 sulfonylureas for diabetes.          a patient's own cells. Dr. Weisel
    Dr. Loscalzo is Chair of          has also investigated techniques to
 Medicine at Brigham and              promote the development of new
 Women's Hospital, a teaching         blood vessels in patients with
 hospital of Harvard Medical          coronary artery disease who
 School. He is also the Editor-in-    cannot undergo coronary bypass
 Chief of Circulation, the leading    surgery.                              "#$!6&'(,#.!7)&1)*!

 Volume 1, Number 1                                                                  Winter 2008

 Scientific Advisory Committee Members
                                                                          Comprised of 7
 2008-9                                                               European and 7 North
                                                                       American experts in
                                                                        cardiology, cardiac
 Dr. Garret Fitzgerald, University of Pennsylvania                   surgery and neurology,
 Dr. Robert Frye, Mayo Clinic                                         the Scientific Advisory
 Dr. Valentin Fuster, The Mount Sinai Medical Center                       Committee is
 Dr. David Ginsburg, University of Michigan/Howard Hughes                 responsible for
   Medical Institute
                                                                     evaluating the scientific
 Dr. Constantino Iadecola, Weill Medical College of Cornell
                                                                        merit of proposals
 Dr. Joseph Loscalzo, Brigham and Women's Hospital                       submitted to the
 Dr. Richard Weisel, Toronto General Hospital                           foundation and for
                                                                    monitoring the progress
 EUROPEAN                                                               of funded research
                                                                        projects. Members
 Dr. Philippe Amouyel, Institut Pasteur
 Dr. Marie-Germaine Bousser, Hôpital Lariboisière                      serve for a term of 5
 Dr: Günter Breithardt, University of Münster                       years and new members
 Dr. Pierre Corvol, Collège de France                                  must come from the
 Dr. Anna Dominiczak, University of Glasgow                         same side of the Atlantic
 Dr. Michel Lazdunski, CNRS/University of Nice Sophia Antipolis      as departing members.
 Dr. Ludwig Karl von Segesser, Centre Hospitalier Universitaire
   Vaudois Lausanne
                                      The Leducq Transatlantic Network on Adaptive and
                                        Maladaptive Signaling in Cardiac Growth and
    Regeneration has recently elucidated the cause of peripartum cardiomyopathy"!

    Peripartum cardiomyo-        colleagues have shown that       patients, bromocriptine
 pathy (PPCM) is character-      an altered form of prolactin,    appeared to aid in the
 ized by acute heart failure     a hormone normally pro-          recovery from PPCM.
 late in pregnancy or early in   duced in pregnant and post-         With these promising
 the postpartum period.          partum women, causes             results, clinical trials will
 PPCM is rare but carries a      PPCM. Among 12 women             begin in Germany and the US
 high mortality rate (15-        with a history of PPCM who       to identify predictors of PPCM
 25%). As the cause of PPCM      became pregnant again,           risk and to test whether
 had been unknown, patients      bromocriptine, a blocker of      bromocriptine is an effective
 were treated with medic-        prolactin release, prevented     treatment.
 ations not specifically aimed   recurrence in all 6 treated         The Network on Adaptive
 at the disease’s mechanism.     patients. In contrast, all 6     and Maladaptive Signaling is
    Using a mouse model, Dr.     untreated patients had           led by Drs. Helmut Drexler
 Denise Hilfiker-Kleiner and     recurrent PPCM. In other         and Jeffery Molkentin.

 Volume 1, Number 1                                                                       Winter 2008

 About Fondation Leducq
     Fondation Leducq was           in an international context,       has funded 19 grants,
 created by Jean and Sylviane       Fondation Leducq hopes to          supporting 120 core and 149
 Leducq in 1996. Having had         encourage innovative               associated members from 16
 business and personal              research, an efficient use of      countries: Austria, Belgium,
 interests in Europe and in the     resources, and the                 Canada, the Czech Republic,
 United States, the Leducqs         development of long-term           Denmark, Finland, France,
 oriented the foundation            collaborations that will           Germany, Israel, Italy, Mexico,
 towards collaborative medical      continue to meet the               the Netherlands, Sweden,
 research, believing that the       challenges of cardiovascular       Switzerland, the United
 battle against cardiovascular      and neurovascular disease.         Kingdom, and the United
 and neurovascular disease              Fondation Leducq awarded       States.
 should be waged at the             its first research grants in          For more information
 international level.               1999. To place greater             about the Fondation, please
     By forging scientific          emphasis on international          visit our website at
 alliances that transcend           collaboration, the Transatlantic
                                                              or contact Dr.
 national borders, and              Networks of Excellence
                                                                       David Tancredi at
 promoting the education of         program was initiated in 2003.
 young researchers who thrive       To date, the Network program

              Fondation Leducq
              1, rue Laurent Pichat
              75116 Paris
              Tel: +33 (0)1 45 00 59 65
              Fax: +33 (0)1 45 00 07 88