The Genes That Protect Against Atherosclerosis, A Major Cause Of Myocardial Infarction And Stroke

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Main Category: Cardiovascular / Cardiology
Also Included In: Stroke / Neuroprotection;  Cholesterol
Article Date: 16 Mar 2008 - 5:00 PDT

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Myocardial infarction and stroke cause nearly half of all deaths in the Western World, and atherosclerosis is the main cause of myocardial infarction and stroke. Scientists from the Karolinska Institutet, Sweden, have shown with mouse models that the accumulation of the plaque that causes myocardial infarction and stroke can be avoided.

You can read about this in the March 14th issue of PLoS Genetic.

The authors write about prevention through reducing levels of bad LDL cholesterol before atherosclerotic plaque has progressed beyond a particular point. A network of 37 genes that reduce levels of blood cholesterol to bring about the beneficial effect has also been identified.

Team leader Johan Björkegren, explained "Previously, much atherosclerosis research was focused on identifying ways to stabilise the most dangerous plaques in order to prevent them rupturing and causing myocardial infarction or stroke. Our discovery means that we can now target the actual development of dangerous plaques. The time when individual genes or gene pathways were thought to explain the development of complex common diseases, such as atherosclerosis, is past. We now have enough tools and knowledge of systems biology to take on the total complexity of these diseases."

The findings indicate that atherosclerosis development does not follow a linear progression, but rather first develops slowly without severe inflammation, then speeds up, and within 10 weeks forms advanced plaques. Bringing down plasma cholesterol just before the rapid expansion can prevent the formation of advanced plaques, says Björkegren. The authors took this information and determined 37 of the atherosclerosis genes that respond to the lowering of plasma LDL and prevent the formation of advanced plaques.

The study offers a comprehensive compendium of gene expression profiles of atherosclerosis development from healthy arteries to arteries with advanced plaques. Björkegren admits there must be more than 37 genes in this network, and thus future studies can focus on adding to this group. Björkegren adds that researchers also need to take these identified genes and use model systems in relevant cell cultures and animal model systems to determine their exact biological roles on atherogenesis.

"Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes"
Skogsberg J, Lundstro¨m J, Kovacs A, Nilsson R, Noori P, et al. (2008)
PLoS Genet 4(3): e1000036. doi:10.1371/journal.pgen.1000036
Link to article online

PLoS Genetics
http://www.plosgenetics.org

The Public Library of Science
http://www.plos.org

Written by - Christian Nordqvist
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