High Blood Pressure Research Council of Australia

HBPRCA Email Newsletter

June 2006

This is our second e-news for the year with quarterly updates rather than monthly. As such we have a lot of developments as the Annual Scientific Meeting takes shape in Queensland (see Jaye’s section). The telemetry workshop is also taking shape for the Wednesday before the meeting sponsored by Data Sciences and will also be held at the Carlton Crest. Please note that last years ASM abstracts will be published in the July issue of CEPP. The feature article this time is the second instalment from the Baker Institute featuring the Vascular Pharmacology and Cardiac Hypertrophy Laboratories. Congratulations to Warwick Anderson who has become the new CEO of the NH&MRC.

The Committee have now updated the ‘Travel grant and Awards’ page on the website. Please click here to view this page, under the meetings section.

Don't forget that the ISH registration deadline is fast approaching.

ISH Notification of Abstract Acceptance: June 15, 2006
ISH Registration Deadline for Presenting Authors: June 30, 2006

PRESIDENT’S MESSAGE from Stephen Harrap

Many of you might have seen the publicity surrounding World Hypertension Day on 13 May. For those of you who didn't, there was a very extensive involvement by members of the Council across Australia with radio, TV and press interviews and comments. I'd like to thank all those members of the Council who put themselves into the firing line and in doing so helped raise the profile of the Council and at the same time delivered an important public health message.

Your Executive, Secretariat and Local Organising Committee have been working hard on plans for the Brisbane Annual Scientific Meeting. It's shaping up as a great event on the calendar. You can read more about this in Jaye's piece.

The other big meeting this year is the ISH meeting in Japan. I hope that all students who have submitted abstracts have also joined as Student Members of the Council (it's free) because it makes them eligible for travel support to this conference.

Enjoy reading e-News!

MEETING NEWS from Jaye Chin Dusting

After a lot of foot-work and site visits, our Brisbane Organising Committee, spearheaded by Malcolm West and Michael Stowasser, have decided on the Carlton Crest as the best location for our Annual Scientific Meeting. They have also chosen the breezy, gorgeously situated River Canteen on the Boardwalk as the place to be for our conference dinner.

In keeping with our Queensland flavour, I am delighted to announce that Prof John Mattick (Institute of Molecular Biology, University of Queensland) has accepted our invitation to attend as our 2006 Austin Doyle Lecturer. Please see below a bio of Prof Mattick, (lifted out of the University of Queensland website).

Professor Mattick was responsible for the development of the IMB with Professor Peter Andrews. In 1988 he was appointed the Foundation Professor of Molecular Biology and Director of the Centre for Molecular Biology and Biotechnology at the University of Queensland.

The Centre was subsequently designated a Special Research Centre of the Australian Research Council (1991-1999) and was re-named the CMCB (Centre for Molecular & Cellular Biology), with its primary focus being the molecular genetics of mammals and their diseases, including genome mapping, gene regulation, developmental biology and cell biology.

He was responsible for the development of one of the first recombinant DNA-based vaccines, and was the recipient of the 1989 Pharmacia-LKB Biotechnology Medal from the Australian Biochemical Society, and the inaugural (2000) Eppendorf Achievement Award from the Lorne Genome Conference. His current research interest is in the role of non-coding RNAs in the evolution and development of complex organisms. He has published over 100 scientific papers.

Professor Mattick is also, among other things, a member of the Australian Health Ethics Committee and the Research Committee of the NHMRC. He is a foundation member of the recently established International Molecular Biology Network (Asia-Pacific), was a foundation member of the Board of ANGIS (the Australian National Genome Information Service) from 1991-2000 and is currently a member of the Board of the Australian Proteome Analysis Facility. He is a member of the Queensland Biotechnology Advisory Council and on the Scientific Advisory Boards of several institutes nationally and internationally. He was appointed as an Officer in the Order of Australia in June 2001.

Spread the word, dairy the dates (Dec 7th and 8th) and be there!

3rd Australian Telemetry Users Group Meeting at the HBPRCA ASM

As the official ASM workshop this year there will be a one-day meeting sponsored by the suppliers of telemetry equipment, Data Sciences International. The event will be on the Wednesday the 6^th of December at the Carlton Crest hotel in Brisbane prior to the ASM. For those currently using the equipment or interested in its potential, the workshop is an ideal time to get to know others in the area and discuss radiotelemetry issues. Data Sciences will be sending representatives for us to engage in what is usually a forthright discussion. Please contact Geoff Head and Dmitry Mayorov for further details.

MEMBERSHIP MESSAGE from Doug McKitrick

Membership information for 2006 will be finalised shortly and it is clear that membership in the HBPRCA has grown dramatically in the case of students. Student membership has more than doubled. So now is a great time to be part of a vibrant, changing and growing scientific society. The helpful email reminders for those of you who haven’t renewed your subscription will soon cease. Of course your ability to renew will not cease and may still be done by mail, fax or internet. If you have internet access go to the HBPRCA website and follow the link for access to the secure payment site, or to download a form for return by fax or post. If you don’t have internet access, can’t remember if you have paid, or just need a bit of help, contact the Secretariat by phone, fax, email or post (details below). And now that you are fully convinced of the brilliance and commitment of your graduate students and post-docs, share them with us by encouraging them to take advantage of HBPRCA membership.

SOCIETY NEWS from Kate Denton

American Council for High Blood Pressure Research (CHBPR)

Negotiations with the CHBPR to foster links between our societies are progressing. Effective immediately, Australians working in the USA are now eligible to apply for travel awards to attend the CHBPR annual meeting. The Leadership Committee of the CHBPR also wishes to encourage Australian investigators to apply for travel awards for future meetings. They have indicated that while no funds are earmarked for Australia (as yet), they do have funds available (on a limited basis) that are not earmarked for a given geographic area. It is their hope several investigators from Australia will apply. I am currently investigating the process through which this source of travel funds can be accessed.

I am attending the CHBPR annual meeting in San Antonio, Texas this October and I have been invited to attend the CHBPR Leadership Committee meeting. It has been suggested that we derive a joint proposal for funding travel awards of scientists from Australia to attend and participate in CHBPR meetings for industry fund raising purposes. Also, discussions will be held on the subject of strengthening the relationship between our councils. Any suggestions from the membership about how this could be achieved would be welcome.

Canadian Hypertension Society (CHS)

Doug McKitrick and I have also been having discussion with CHS. The CHS executive, have meet with enthusiasm our initial overtures and are keen to establish some exchange between the CHS and HBPRCA. With the ISH2010 taking place in Vancouver, we are exploring the possibility of initiating some collaboration from both sides between 2006 and 2010.

JUNE FEATURE ARTICLE

Vascular Pharmacology at the Baker Heart Research Institute

The focus of the lab is on translational research addressing questions of significance in the prediction, diagnosis and treatment of cardiovascular diseases. Atherosclerosis remains the major underlying aetiology for cardiovascular disease. Our work in atherosclerosis is directed at the emerging areas of inflammation, immunology and cell adhesion. Other studies investigate the development and consequence of new vessel growth within atherosclerotic plaques. A new area of interest is the dependence on the presence of circulating endothelial progenitor cells as well as putative differences between diabetic and non-diabetic states. Recent studies have revealed a role for circulating adhesion molecules and the importance of these will be examined in human vessels. Lipids, hypertension and diabetes remain central to the development of clinical atherosclerosis. Our clinical lipid studies focus on HDL cholesterol and the anti-inflammatory effect of HDL on monocytes. Peripheral artery disease (PVD) presents a considerable clinical burden and also the opportunity to pursue mechanistic studies in a less precarious environment than in the coronary circulation. Current studies are involved in examining therapeutic options and the role of adhesion molecules in PVD. Other projects include studies on the role of arginase where we are examining possible mechanisms by which intracellular levels of L-arginine may be affected by competing catabolic pathways. Arginase, which catabolises L-arginine to form ornithine and urea, is one such pathway and has been shown to contribute to endothelial dysfunction in hypertension and aging blood vessels. Our current studies demonstrate that arginase inhibition conserves intracellular L-arginine stores, not only preserving endothelium nitric oxide responses in healthy vessels but preventing nitrate tolerance possibly through reducing eNOS uncoupling and regulating superoxide production. We propose to extend these investigations by deciphering the role of each arginase isoform using isoform specific knockout mice and isoform specific in vivo adenoviral transfection studies. Our preliminary data suggests a novel arginase II- RhoK pathway which may underlie the enzymes anti-hypertensive properties. Finally we have a substantial program on correcting the haemodynamic abnormalities in patients with liver cirrhosis. Current studies include the use of probiotics as a therapeutic intervention; extending our previous work on antibiotics in this patient population.

(from L to R: April Toh, Laura Willems, Emma Jones, Ann-Maree Jefferis, Ngan Huynh, Rajesh Nair, Jaye Chin-Dusting, Andrew Murphy, Margaret Vincent, Nathan Connelly, Kevin Woollard)

Recent Publications

Boak L, Dart A, Duffy S and Chin-Dusting. Neither responses to endogenous nor exogenous endothelin-1 are altered in patients with hypercholesterolemia. Journal Lipid Research, 46; 2667-2672, 2005.
Chin-Dusting J, Mizrahi J, Jennings G, Fitzgerald D. Outlook: finding improved medicines: the role of academic-industrial collaboration. Nature Reviews Drug Discovery, 4:891-7, 2005.
Woollard KJ, Kling D, Kulkarni S, Dart A, Jackson S and Chin-Dusting J. Raised plasma soluble P-selection in peripheral arterial occlusive disease enhances leukocyte adhesion. Circulation Research; 98: 149-56, 2006.
Chin-Dusting JPF, Shennan J, Jones E, Williams C, Kingwell B and Dart A. Effect of Dietary Beta Casein A1 or A2 on Surrogate Markers of Disease Development in Persons at High Risk of Cardiovascular Disease, British Journal of Nutrition, 95; 136-144, 2006.
Sviridov D, Chin-Dusting J, Nestel P, Kingwell B, Olchawa B, Hoang A, Starr J & Dart A. Elevated HDL Cholesterol is Functionally Ineffective in Cardiac Transplant Recipients: Evidence for Impaired Reverse Cholesterol Transport. Transplantation 2006;81(3):361-6, 2006.

Cardiac Hypertrophy Laboratory: Dr Julie McMullen

Julie obtained her PhD at the University of NSW and completed a postdoctoral research fellowship at Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA before joining the Baker early in 2005.

The lab focuses on understanding heart enlargement, cardiac hypertrophy, through comparisons between models of health and disease: examining the enlarged athletic heart in comparison to heart enlargement associated with disease.

It is well understood that the hearts of athletes grow: the super fit have a heart size greater than the average person. This enlargement is of benefit to them in their training and works to enable them to continue their level of exercise and fitness. When they stop training that healthy heart growth stops and the heart returns to a normal size. Conversely, heart failure patients commonly experience heart growth but this change is devastating, wreaking havoc and usually impossible to reverse.

From this observation, Julie’s research has focused on understanding the changes in the athlete’s heart that might benefit people with heart disease, whose heart growth might be caused by hypertension and/or heart failure.

Julie’s studies demonstrate there are changes in genes that occur in people with cardiac hypertrophy associated with heart failure that do not occur in the athlete’s heart: she has established that even though there are comparable increases in heart size, there are clear molecular and histological changes between the two.

The lab is working to identify genes causing heart enlargement that are good for the heart, as opposed to those genes causing heart enlargement with detrimental effects. In doing so she hopes to reproduce the work of the “good genes” in the failing heart.

The research area is novel in its suggestion that it is possible to promote and activate “good” genes in the heart as opposed to just inhibiting “bad” genes that cause the growth of the diseased heart. Julie’s research involves genetically modified mouse models of heart failure. By over expressing a gene involved in the growth of the athlete’s heart in a mouse model with heart failure, she hopes to understand whether this gene might be of use to patients with heart disease, and whether its promotion and growth can negate the effects of the “bad” growth genes.

Recent Publications

1. McMullen JR, Sadoshima J, Izumo S. Physiological versus pathological cardiac hypertrophy. In: Molecular Mechanisms of Cardiac Hypertrophy and Failure, edited by Walsh RA. London: Taylor & Francis, 2005, p. 117-136.

Luo J*, McMullen JR*, Sobkiw CL, Zhang L, Dorfman AL, Sherwood MC, Logsdon NM, Horner JW, DePinho RA, Izumo S and Cantley LC. Class IA Phosphoinositide 3-Kinase Regulates Heart Size and Physiological Cardiac Hypertrophy. Mol Cell Biol 25: 9491-9502, 2005.

*The first two authors should be regarded as joint first authors.

3. McMullen JR, Shioi T, Zhang L,Tarnavski O, Sherwood MC, Dorfman AL, Longnus S, Pende M, Martin KA, Blenis J, Thomas G and Izumo S. Deletion of ribosomal S6 kinases does not attenuate pathological, physiological or IGF1R-PI3K induced-cardiac hypertrophy. Mol Cell Biol. 24: 6231-6240, 2004.

4. McMullen JR, Sherwood MC, Tarnavski O, Zhang L, Dorfman AL, Shioi T, and Izumo S. Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. Circulation 109: 3050-3055, 2004.

HBPRCA Secretariat

Athina Patti at

Meetings First

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