Tuesday 12 May 2009

Award winning research at the Dutch Atherosclerosis Symposium, 2009

The years to come are going to be very busy for persons working in the field of atherosclerosis and cardiovascular disease. Basic-science researchers are hot on the trail of targeted drugs that will be much more focused than available drugs, and some remarkable progress is being made. The 12th Dutch Atherosclerosis Symposium took place on March 12 and 13, 2009 and showcased some of this progress taking place in the Netherlands. I would like to briefly present 4 of the interesting research topics that received jury awards.

Exercise
Meissner et al.1 investigated the effect of exercise on cholesterol metabolism in mice either exposed to voluntary running wheel for 2 weeks or which remained sedentary. Exercise appears to increase cholesterol and bile acids turnover via specific changes in the intestine that decrease intestinal bile acid and cholesterol absorption and promote their fecal excretion. If the same holds true in humans, exercised-induced modulation of bile acids and cholesterol turnover leading to reduced plasma cholesterol levels might contribute to the beneficial effects of exercise on cardiovascular disease.

Cathepsin inhibition
The research aim of Waard et al.2 is to develop pharmaceutical therapies for abdominal aortic aneurysm to prevent surgical intervention in elderly patients. They have previously shown that cathepsins are functionally involved in collagen degradation in human aneurysm tissue. In the present study they showed that E64 (a cathepsin inhibitor) treatment resulted in a decreased number and severity of aneurysms and in a less inflammatory profile in serum in a mouse model. The inhibition of cathepsins may be therefore an attractive therapeutic approach to prevent aortic aneurysms expansion.

Microarray antigen chip
The immune system is thought to play an important role in initiation and progression of atherosclerosis. Den Dekker et al.3 aimed to explore the potential of auto-antibody profiles as a biomarker for a cardiovascular event. A generic version of the antigen microarray was used bearing over 740 proteins related to a variety of conditions including immune regulation, inflammation, angiogenesis, apoptosis and more. The antigen microarray was able to identify patients with previous myocardial infarction with a high sensitivity and specificity. In conclusion, a microarray antigen chip may be used as a novel biomarker for cardiovascular disease.

Nuclear receptor Nurr1
Bonta et al.4 have investigated the role of nuclear receptor Nurr1 in stent restenosis. They found that Nurr1 is expressed in human in-stent restenosis lesions. Nurr1 inhibits inflammatory gene expression in both macrophages and smooth muscle cells and it inhibits proliferation of smooth muscle cells. In vivo Nurr1 reduces neointima formation in mice. Small-molecule drugs have been identified that enhance the transcriptional activity of this nuclear receptor. It seems therefore that Nurr1 may be an attractive novel target for local intervention against in-stent neointima formation.

Comment
Genetics and biochemistry have now become the unchallenged leaders of cardiovascular research. New drugs to be soon perfected together with the immense progress in the invasive field will completely change the cardiology that we all knew.

By: Sandrin C. Bergheanu, MD, Dept. of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (s.c.bergheanu@lumc.nl)

References

1. Maxi Meissner et al., Department of Pediatrics, University Medical Center Groningen, The Netherlands. E-mail: M.Meissner@med.umcg.nl

2. Vivian de Waard et al. Division of Biopharmaceutics of the Leiden/Amsterdam Center for Drug Research, Leiden and Department of Medical Biochemistry, AMC, Amsterdam, The Netherlands. E-mail: v.dewaard@amc.uva.nl

3. Wijnand den Dekker et al. Molecular Cardiology Laboratory, Erasmus Medical Center Rotterdam, The Netherlands.

4. Peter Bonta et al. Department of Medical Biochemistry, Academic Medical Center Amsterdam, The Nertherlands. E-mail: P.I.Bonta@amc.uva.nl

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