Jahresbericht der Klinik - Klinik für Kardiologie - UniversitätsSpital ...

Thomas F. Lüscher, MD
Primary Investigator
Ulf Landmesser, MD
Primary Investigator
Michaela Keel, M. Sc.
Project Coordinator
Special Program: Leducq Network
A Transatlantic Network of Excellence
on HDL Dysfunction
In October 2010 we started an international transatlantic network
of excellence in cardiovascular research, funded with USD 6 million
by the Leducq Foundation. This program is focused on high density
lipoprotein (HDL) as a potential novel therapeutic target in cardiovascular
therapy.
Low levels of HDL cholesterol are associated with an increased cardiovascular
risk and experimental studies suggest potential anti-atherogenic
properties of HDL. Therefore, several clinical trial programs
are currently testing different approaches to raise HDL cholesterol as
a novel therapeutic strategy to reduce cardiovascular events. The first
major trial, the ILLUMINATE study pointed to potential difficulties
of this approach. In this trial there were more cardiovascular events
using torcetrapib-therapy to inhibit the cholesterol esther transfer
protein (CETP) that has been attributed to off-target effects of this
substance. Large clinical outcome trials are underway using other
CETP inhibitors without off-target toxicity.
At our institution we could also demonstrate that the quality of HDL
is altered in patients with coronary artery disease. We are currently
working together to identify underlying molecular mechanisms causing
this so-called «dysfunction of HDL» in patients with coronary disease
and to understand its clinical implications within this network.
In 2011 we held two network meetings which were focussed on
vascular effects of HDL and HDL as a therapeutic target. These meetings
were held in New York at Columbia University [Fig. 1] and in
Lenzerheide, Switzerland [Fig. 2]. There is intensive interaction and
exchange among the network sites at the Columbia University in
New York, Cleveland Clinik and University of California in Los Angeles,
as well as the University College in London, and the University
Hospital Zurich to address these urgents research questions.
1. *Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM,
Chroni A, Yonekawa K, Stein S, Schaefer N, Mueller M, Akhmedov A,
Daniil G, Manes C, Templin C, Wyss C, Maier W, Tanner FC, Matter CM,
Corti R, Furlong C, Lusis AJ, von Eckardstein A, Fogelman AM,
Lüscher TF, Landmesser U.
Mechanisms underlying adverse effects of HDL on eNOS-activating
pathways in patients with coronary artery disease.
J Clin Invest. 2011; 121(7):2693 – 2708
2. *Caron S, Verrijken A, Mertens I, Samanez CH, Mautino G, Haas JT,
Duran-Sandoval D, Prawitt J, Francque S, Vallez E, Muhr-Tailleux A,
Berard I, Kuipers F, Kuivenhoven JA, Biddinger SB, Taskinen MR,
Van Gaal L, Staels B.
Transcriptional activation of apolipoprotein CIII expression by glucose
may contribute to diabetic dyslipidemia.
Arterioscler Thromb Vasc Biol. 2011; 31(3):513 – 9
3. *Murphy AJ, Akhtari M, Tolani S, Pagler T, Bijl N, Kuo CL, Wang M,
Sanson M, Abramowicz S, Welch C, Bochem AE, Kuivenhoven JA,
Yvan-Charvet L, Tall AR.
ApoE regulates hematopoietic stem cell proliferation, monocytosis,
and monocyte accumulation in atherosclerotic lesions in mice.
J Clin Invest. 2011;121(10):4138 – 49
Fig. 1 Network Meeting at the Columbia University, New York, May 2011 Fig. 2 Network meeting in Lenzerheide, Switzerland, January 2012