|
|
AAS Quarterly E-Newsletter
July 2010
|
|
Already half-way
through 2010 and now it is those dreaded three, RMS and four letters, RGMS, that
occupy our thoughts as we assess and rebut. Again we find ourselves spending
too much time on grant processes with less time spent in the laboratory
grappling with our scientific endeavours. One of the key things in Australian
science is to keep our “up and coming” Early Career Scientists motivated, so
for this newsletter we asked an early post-doctoral scientist to tell us
about her research. Dr Joanne Tan works at the Heart Research Institute in Judy de Haan and
Alison Heather, July 2010 |
|
President's Report As you know, the
next annual meeting is the Asian Pacific Society of Atherosclerosis and
Vascular Diseases in Cairns from 26-29th of October which AAS is hosting and
which will also be the 2010 AAS Annual Scientific Meeting with special sessions
run in partnership with the Australian Diabetes Society and the European
Atherosclerosis Society. The program is coming together and we are getting
interest from delegates from around the world. Click here
for details.
Abstracts close on July 15, so please submit your abstract via www.meetingsfirst.com.au now! Don’t forget to book flights early to get the cheapest deals.
Students
and supervisors please note: The AAS Education
Subcommittee plans to develop interim guidance on lipid management by updating
Australian Public Position Documents such as NHF guidelines. It aims to
do this by considering the implications of recently completed lipid trials. If you would
like to be a member of the committee established to develop these documents, Congratulations also to Kerry Rye and the team
preparing for ISA2012. Their presence in Hamburg for EAS did not go
unnoticed. To help promote the meeting, please include this
slide at
the end of any presentation you are giving over the next year. |
|
HIGHLIGHTING YOUNG ACHIEVERS
– Dr Joanne Tan
Alzheimer’s
disease is a progressive neurodegenerative disease that affects the brain,
resulting in impaired memory, thinking and behaviour. It is the most common
form of dementia, accounting for 50% - 70% of all reported cases. The cause
and progression of Alzheimer’s disease is not well understood. There is
increasing evidence suggesting a link between Alzheimer’s disease and
cardiovascular diseases, especially atherosclerosis. The presence of
Alzheimer’s disease neuropathology hallmarks in many post mortem cases of
non-demented coronary artery disease (CAD) indicate that CAD could be a
possible risk factor for the development of Alzheimer’s disease. In addition,
it has also been shown that the dominant mechanisms implicated in the
development of atherosclerosis, namely hypercholesterolaemia and
inflammation, have also emerged as key factors involved in the pathogenesis
of Alzheimer’s disease. In
2000, a new gene known as seladin-1 (for selective Alzheimer’s disease
indicator-1) was identified and found to be down regulated in vulnerable
brain regions of Alzheimer’s disease patients. This gene was found to be
identical to the gene that encodes for the endoplasmic-reticulum resident
protein, 3b-hydroxysteroid-D24 reductase (DHCR24), an
enzyme that catalyses the final step in the cholesterol synthesis pathway,
converting desmosterol to cholesterol. Studies have highlighted that
cholesterol plays a crucial role in maintaining brain homeostasis. With this
in mind, DHCR24 has been studied extensively within this context and has been
found to be a fundamental mediator of the protective effects of estrogens in
the brain. More recently studies have suggested that, in addition to its role
in cholesterol biosynthesis, DHCR24 is a multifaceted protein that is
important in regulating inflammation, oxidative stress and apoptosis in
neuronal and fibroblast cells. High
density lipoprotein (HDL), otherwise known as the “good cholesterol”, has
long been established to have protective effects against the development of
atherosclerosis. HDL suppresses inflammation in human coronary artery
endothelial cells (HCAECs). This effect persists even if the HDL is removed
several hours prior to activation of HCAEC, suggesting that HDL induces the
expression of a protein with the potential to protect against a subsequent
inflammatory insult. Using a microarray approach, we identified DHCR24 to be
one of the most up-regulated genes by HDL pre-incubation. Furthermore, when
DHCR24 levels were knocked down in HCAECs, HDL loses its anti-inflammatory
effects. These findings suggest that the anti-inflammatory effects of HDLs
are mediated through an up-regulation of DHCR24. We
continued to explore the role of DHCR24 in HCAECs and hypothesised that low
DHCR24 levels would direct endothelial cell dysfunction, increasing both the
inflammatory and oxidative state in these cells, thereby predisposing the
cells to apoptosis. We confirmed that knockdown of DHCR24 increases the
expression of inflammatory genes such as VCAM-1 and ICAM-1 and that the
inflammatory response induced by low DHCR24 levels is due to its role as an
antioxidant and not via the changes in the cholesterol synthesis pathway. Furthermore,
there was an increase in oxidative stress in cells that had low DHCR24 levels
triggering an ER stress response. The induction of both an inflammatory and
oxidative stress response in knockdown DHCR24 cells activated apoptosis.
Collectively, our results provide evidence that DHCR24 appears to mediate
several cellular processes that are important in maintaining endothelial cell
function. In
addition, we measured the expression of DHCR24 levels in the aortic arch of
an animal model of atherosclerosis, the Apolipoprotein E knockout (ApoE-/-)
mouse model. In this study, we found that low DHCR24 levels were associated
with atherosclerotic lesion development in ApoE-/- mice. Apolipoprotein E is
a key regulator of plasma lipid levels, affecting all lipoproteins either
directly or indirectly via the modulation of their receptor-mediated
clearance or lipolytic processing and the production of hepatic very low
density lipoproteins. It was originally recognised for its importance in
cardiovascular disease but has now emerged as an important molecule in
several biological processes unrelated to its lipid transport function, one
of which is its link to Alzheimer’s disease. ApoE is a polymorphic protein
and has three major isoforms namely ApoE2, ApoE3 and ApoE4. In the context of
Alzheimer’s disease, it has been shown that the ApoE4 allele is the major
susceptibility gene related to the occurrence and early age of onset of
Alzheimer’s disease. For
now, the link between atherosclerosis and Alzheimer’s disease is slowly being
elucidated and based on the data we have generated; it may be that DHCR24 and
ApoE to be major players in the link. These findings have potential
implications for treating inflammation associated with atherosclerosis that
would prove beneficial not only for patients susceptible to coronary heart
disease but also to patients with Alzheimer’s disease. Joanne
Tan |
|
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. Remember – if you are not a
financial member BEFORE registering for the ASPAVD-AAS meeting in Cairns, you
will not be eligible for the discounted members rates. The Australian Atherosclerosis Society always
welcomes new members. Please encourage your students and work colleagues to
join the AAS. Remember, that members receive the 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 |
|
FH Corner – Gerald
Watts Greetings from
Oxford! While overseas for a few months, we have continued developing the
Model of Care and developing relationships with like-minded organisations
overseas. We have also recently re-activated the review of the FH section of
the AAS website, and plan to have a more patient-friendly version operational
later this year. |
|
|
|
Forthcoming Meetings 23rd Scientific Meeting of
the International Society of Hypertension 26 – 30 September 2010 Click here
for more information AAS ASM-APSAVD Congress 2010 26
– 29 October 2010, Cairns, Australia Click here
for more information ISA 2012 26
– 29 March 2012, Sydney, Australia Click here
for more information IAS2012 – get your slide here! |
|
International
Atherosclerosis Society Click here
for Highlights from the Satellite, “High Density Lipoproteins and
Atherosclerosis” held on June 19-20, 2009 Please click here to
view the May E-Newsletter. |
|
E-News If there is information you would like to include
in the next e-news, please email it to aas@meetingsfirst.com.au by Friday
30 July 2010. AAS Secretariat Jennifer Seabrook PO Box 448 Yarra Junction VIC 3797 Phone +61 3 5967 4479 Fax +61
3 9015 6409 Email aas@meetingsfirst.com.au |
