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AAS Quarterly
E-Newsletter
June
2007
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Welcome
once again to all AAS members. In our journey around Australia we stop at
Melbourne at Dmitri Sviridov’s group at the Baker. As well as the usual
updates, there is another reminder that the deadline for abstracts for AAS
ASM 2007 draws ever closer. On behalf of the Executive we encourage as many
members as possible to make the trip to Fremantle and help us showcase the
exciting and innovative research the AAS is recognised for. Cheers |
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President's
Report The executive is
making headway in establishing an AAS educational programme. A meeting with major pharmaceutical sponsors
in April progressed a proposal to host an annual, 1-day educational meeting,
alternating between Melbourne and Sydney, and aimed at specialists and
selected registrars and general practitioners. A half-day educational meeting
adducted to the annual scientific meeting in different states is also
proposed. A final round table discussion with industry will be held at the
time of the annual scientific meeting in Perth to agree and finalise the
support for this programme. It would appear
that the AAS is developing four major areas of activity: science and
research, education, health care services, and income generation. Science and
research currently centres on the annual scientific meeting. Educational
activities are being developed and at present aim at the translational level.
Patient services focus on familial hypercholesterolaemia via the FH
sub-committee. Income generation and promotion of the society are closely
linked with the preceding activities. This four segment organisational
strategy may increase the value and growth of the society, but requires
further discussion and agreement amongst the executive. The
European Atherosclerosis Society Annual Scientific meeting was held in
Helsinki, Finland, in early June. It was pleasing to see a major focus in the
sessions devoted to young investigators from diverse countries. Debates,
sessions on new research techniques such as metabolomics, and workshops on
how to improve the care of familial hypercholesterolaemia were in my view
especially attractive. A particularly apposite gesture of the organising
committee was to name the lecture halls in honour of past-distinguished
members of the society, including Nikilla, Eisenberg, Davies and Erkelens.
Congratulations to Professors Taskinen and Ehnholm on organising a very
eclectic and highly enjoyable meeting in the setting of a beautiful city
basking in balmy summer weather. This then sets the
scene for the next EAS in Turkey in 2008, followed by the ISA in Boston in
2009. By that time we should be consolidating our own plans for the ISA
meeting in Sydney in 2012. Preliminary meetings of the local steering
committee are already being arranged by Kerry –Anne Rye in 2007 and we will
keep you posted about plans and developments. Best wishes |
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Feature
Article Laboratory of Lipoproteins and Atherosclerosis at the Baker Heart Research Institute, Melbourne The Laboratory of
Lipoproteins and Atherosclerosis is one of the oldest laboratories at the Baker
Institute. Prof. Paul Nestel established it in 1976, when he moved his
laboratory from ANU in Canberra to join Prof. Paul Korner in the “new” Baker.
A few years later the laboratory was re-named the Laboratory of
Cardiovascular Metabolism and Nutrition and became one of the largest
laboratories at the Baker. In 1985 Paul Nestel moved to Adelaide to head the
Division of Human Nutrition in CISRO. The laboratory was re-named the
Laboratory of Protein Chemistry and was headed for the next 15 years by Prof.
Noel Fidge. In 1995 the laboratory reverted to its original name, Laboratory
of Lipoproteins and Atherosclerosis. In 2000, Dr. Dmitri Sviridov became head
of the laboratory. In 2005 the laboratory merged with the Laboratory of
Clinical Nutrition bringing back into the laboratory its founder, Prof. Paul
Nestel.
From the beginning
the major research interest of the laboratory was lipoprotein turnover
measured by isotope kinetics and the effects of nutrients and drugs. The focus
on HDL and reverse cholesterol transport developed through research into the
turnover of the HDL apolipoproteins and total body cholesterol flux. Norman
Miller, who published the seminal paper on the link between HDL and coronary
heart disease in the mid-1970s, was a member of the laboratory. Paul Nestel
is one of the founders of the “HDL field”; he recognised the importance of
this lipoprotein fraction and reverse cholesterol transport long before it
moved to the forefront of lipid and lipoprotein research. The goal of the
laboratory remains to develop knowledge of the mechanisms of cholesterol
trafficking in cells and in plasma and to apply this knowledge for developing
new approaches for the treatment of atherosclerosis. The laboratory actively
collaborates with a number of research centres in Australia and overseas
combining efforts toward achieving these goals. Cholesterol efflux
Cholesterol efflux
is the first and most likely the rate-limiting step of reverse cholesterol
transport. It is responsible for removing excessive cholesterol from
macrophages preventing cholesterol accumulation and formation of foam cells.
It is also a key element in the formation of HDL in the liver and intestine.
There are several pathways of cholesterol efflux; the relative contribution
of each pathway most likely depends on cell type and particular metabolic
circumstances. We recently showed that a group of pathways related to
cholesterol efflux to lipid-free apolipoprotein A-I plays the key role in
cholesterol efflux from macrophages in
vitro and in vivo. One such
pathway is the ABCA1-dependent pathway. To further investigate this pathway
we developed a panel of monoclonal antibodies against ABCA1 capable to
specifically inhibit or enhance ABCA1 function. In a collaborative work with
laboratories of Vascular Pharmacology (Dr. J. Chin-Dusting) and Clinical
Physiology (A/Prof B. Kingwell) we used these antibodies to show the role of
ABCA1 in mediating a number of HDL functions. In collaboration with the
Macrophage Biology Group at UNSW (Prof. W. Jessup) we are investigating the
interaction between ABCA1 and ABCG1 transporters in the cholesterol efflux
pathway. In collaboration with the Centre D’Immunologie de Marseille Luminy,
Marseille, France (Prof. G. Chimini) we are investigating interaction between
ABCA1 and ABCA7 transporters in cholesterol efflux. HDL in health and disease
Another direction
in the laboratory research is the pathophysiology of reverse cholesterol
transport in various diseases. The role of impairment of reverse cholesterol
transport in elevating the risk of atherosclerosis is underestimated in a
number of diseases. One of these diseases is HIV infection, which is
associated with a sharply elevated risk of atherosclerosis. In collaboration
with the Department of Immunology and Infectious Diseases, George Washington
University, Washington, DC, USA (Prof. M. Bukrinsky) we recently established
that HIV virus interferes with intercellular cholesterol trafficking shutting
down the ABCA1-dependent cholesterol efflux pathway in macrophages and
causing cholesterol accumulation in these cells. In collaboration with the
Department of Infectious diseases, Alfred Hospital we also uncovered
mechanisms underlying HIV-induced changes in the metabolism of plasma lipoproteins
that may contribute to dyslipidaemia in HIV patients. In collaboration with
the Laboratory of Neuropharmacology (A/Prof. G. Head), Department of Surgery,
Alfred Hospital (A/Prof. J. Dixson) and Department of Medicine, UWA (Prof. G.
Watts) we are also investigating the effects of obesity and weight loss on
reverse cholesterol transport. Collaborating with the Laboratory of Diabetic
Complications we recently completed a study on the effect of diabetes, and
more specifically of advanced glycation end product modification, on reverse
cholesterol transport and functionality of apoA-I. In collaboration with the
Laboratory of Clinical Physiology (A/Prof B. Kingwell) we continue a series
of studies on the effect of exercise on plasma lipoprotein metabolism and the
contribution of these changes to the atheroprotective potential of exercise.
In collaboration with the Department of Immunology, Singapore General
Hospital (Prof. E. S. Tai) we are participating in a study on the effect of
genetic polymorphism in CETP and hepatic lipase on reverse cholesterol
transport. “HDL Therapy”
The ultimate goal
of investigating HDL metabolism is to apply this knowledge for developing an
“HDL therapy” – a way to raise HDL levels in order to increase protection
against atherosclerosis. For a number of years we collaborated with Hoffman
La Roche in studying a CETP inhibitor in
vitro and in vivo settings.
This area has become controversial after the unexpected failure of a clinical
trail of Torcetrapib, the CETP inhibitor from Pfizer. It is still unclear if
the properties of the specific compound, Torcetrapib, are responsible for
this failure or whether CETP inhibition was responsible for the unexpected
adverse effects. Our studies demonstrated the complexity of the relation
between CETP inhibition and stimulation and the efficiency of reverse
cholesterol transport. Both CETP inhibition and stimulation can inhibit or
enhance reverse cholesterol transport depending on metabolic circumstances
showing that CETP inhibitors may be an effective, but not “one size fits all”
solution for low HDL. In collaboration with AstraZeneca and the Department of
Medicine, UWA (Prof. G. Watts and A/Prof. H. Barrett) we investigated the
effects on HDL metabolism and HDL functionality of another drug capable of
raising HDL, rosuvastatin. In a newly developed collaboration with the
Lipoprotein Section of the National Heart Lung and Blood Institute, NIH,
Bethesda, USA (Prof. A Remaley) we entered another promising field of “HDL
therapy”, apoA-I mimetic peptides. New peptides are created at NIH and their
properties in vitro and in vivo are investigated in a joint
project between our laboratory and the laboratory of vascular physiology (Dr.
J. Chin-Dusting). Finally our laboratory is part of a large collaborative project
spearheaded by A/Prof B. Kingwell investigating metabolic consequences of
infusing reconstituted HDL in humans. Commercial activity
The laboratory is
also involved in a number of commercial projects. Joining forces with the
laboratory of Vascular Pharmacology (Dr. J. Chin-Dusting) we developed what
we call the “HDL functionality platform”: a series of tests determining
functional properties of HDL or compounds modelling their function. The
platform is designed to analyse both plasma from patients and animals treated
with the compounds that affect HDL and reverse cholesterol transport, and the
compounds themselves. The platform offers in
vitro, ex vivo and in vivo
tests comprehensively characterising the effect of treatment on HDL
functionality or capacity of the compounds to mimic HDL functions. |
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Australian
Atherosclerosis Society 2007 Annual Scientific Meeting Maritime Museum, Fremantle, Western Australia Plans for the 2007 Annual
Scientific Meeting in Fremantle, to be held from the 23rd to 26th October,
are progressing smoothly. All of the invited speakers have confirmed their
attendance and participation, which should make for an exciting scientific
meeting. The Committee is looking forward to receiving conference abstracts
and putting together the scientific program. A reminder that abstracts are due by the
31st August and early-bird registrations are due by the 7th September. See you in Fremantle. Chairman of the Local Organising Committee |
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Familial
Hypercholesterolaemia (FH) Corner – What else is there? Familial Hypercholesterolaemia (FH) is a common dominant
genetic cause of elevated cholesterol and increased risk of cardiovascular
disease (CVD), but doctors need to consider differential diagnoses by asking
themselves the question: “What else could it be?” Non-specialists often
diagnose FH incorrectly by relying on the combination of increased
cholesterol and the presence of high cholesterol levels in a relative. Like
hypercholesterolaemia in general, this situation usually arises due to a
non-specific mixture of environmental (especially dietary) and genetic
factors. FH should account for no more than 0.3% of the population and it is
usually associated with premature CVD and elevated LDL cholesterol in
approximately 50% of close family members. Physical signs such as early
corneal arcus and tendon xanthomas are not sensitive because they affect less
than one-third of cases. Tendon xanthomas are still helpful because they are
fairly specific, however they can be confounded by tendon rupture or
tendonitis. The only other causes are rare lipid disorders such as
cerebrotendinous xanthomatosis (a disorder of bile acid metabolism),
sitoterolaemia (a disorder of ABC-G5 or G8) and remnant dyslipidaemia (an
accumulation of chylomicron and VLDL remnants). All are due to recessive
disorders, but the Apo E2:E2 genotype underlying remnant dyslipidaemia is
quite common. It only causes the disorder to be expressed when there is an
additional lipoprotein abnormality such as occurs following the development
of obesity, diabetes or hypothyroidism. Other features associated with
remnant dyslipidaemia are a mixture of hypercholesterolaemia and
hypertriglyceridaemia, severe peripheral vascular disease, tuberous xanthomas
and palmar striae. Another genetic cause of grossly elevated lipid levels is
lipoprotein lipase deficiency. This causes massive triglyceride elevation
that can trigger a dangerous episode of acute pancreatitis. It is another
rare recessive disorder. Massive hypertriglyceridaemia can also arise when
common hypertriglyceridaemia is exacerbated by diabetes, alcohol excess or
high fat diet. Other genetic causes of hyperlipidaemia have become less
certain. Inheritance of isolated hypertriglyceridaemia is uncommon and early
suspicions that this may represent a defect in bile acid resorption have not
been substantiated. Inheritance of
increased apolipoprotein B secretion which can cause hypercholesterolaemia,
hypertriglyceridaemia or a combination of both is referred to as Familial
Combined Hyperlipidaemia. It has no distinctive physical features and its
existence as an independent condition has become controversial because it
overlaps with the insulin resistance syndrome. There are other inherited
lipid disorders that cause low, rather than high lipid levels. Nevertheless
they are informative because some of them are associated with premature CVD.
Inherited metabolic disorders should always be seen as a unique opportunity
to increase our understanding of common disease processes such as CVD. |
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Membership
News If you have not
renewed your membership, please click here to visit the Meetings
First website and renew online. Alternatively, please click here to
download a copy of the paper registration form. |
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The
Australian Atherosclerosis Society always welcomes new members. Please
encourage your students and work colleagues to join the AAS. Remember, that
members receive thew following: -
A monthly email that
includes, job opportunities, information on meetings relating to
atherosclerosis and regular updates on similar interests. -
A new quarterly
newsletter that will feature different articles each quarter. -
Discounted rates to attend
AAS Annual Scientific Meetings. -
Networking opportunities
and involvement. -
Opportunity to receive
student travel grants and present your research at the Annual Scientific
Meeting. -
Opportunity to apply for
AAS Trust travel grants |
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Forthcoming
Meetings Japan Atherosclerosis Society 39th Annual Meeting 13-14 July 2007, Osaka, Japan For more information please click here to
send the JAS an email. 10th Annual Scientific Forum of the Southeast Lipid
Association 3-5 August 2007,
Savannah, GA Please click here for more information on
this meeting. XVI International Symposium on Drugs Affecting Lipid
Metabolism 4-7 October 2007, New
York Please click here for more information on
this meeting. IAS Workshop on HDL 2007 9-12 October 2007,
Santorini, Greece A
full program is now available! Click here to
download. Please click here
for more information on this meeting. The 2nd International Conference on
Frontiers in Vascular Medicine 26-28
October 2007, Melbourne Please click here for more information on this
meeting. 4th Joint Meeting of the Society For Free Radical Research
Australasia and Japan 1-5 December 2007,
Kyoto, Japan For more information please click here to email the organisers. Future APSAVD Congresses The
6th APSAVD Congress will be hosted in Hong Kong in 2008. It will be held at the
beginning of October coinciding with Chinese National Day and a fantastic
fireworks show on the Harbour near the Convention. The 7th APSAVD
Congress will be hosted in Australia in 2010. |
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International Atherosclerosis Society Please click here to
view the June E-Newsletter. |
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E-News The
next E-News will be sent out on 16 July 2007. If there is information you
would like to include, please email it to aas@meetingsfirst.com.au
by Wednesday 11 July 2007. Please
do not hesitate to contact me if you have any queries. Kind
Regards, AAS
Secretariat 4/184
Main Street Lilydale
VIC 3140 Phone
+61 3 9739 7697 Fax +61 3 9739 7076 Email aas@meetingsfirst.com.au |
