05 February 2018

A widely used anti-asthmatic drug can slow the development of aortic aneurysms in mice, according to a study carried out by researchers at Karolinska Institutet and Linköping University. The results have been published in the prestigious medical journal PNAS.

3D illustration of the heart Photo credit: yodiyim
"These are extremely interesting results and we now have additional drug candidates in the pipeline that we may use in trials," says Dick Wågsäter, professor at the Department of Medical and Health Sciences at Linköping University and one of the researchers who conducted the study.Dick WågsäterDick Wågsäter, professor Photo credit: Emma Busk Winquist

Dick Wågsäter focuses his research into aortic aneurysm. This condition occurs when a bulge forms in the wall of part of the largest blood vessel in the body, the aorta. The blood vessel wall becomes weak and extends. The aneurysm bursts in some cases and the risk of death from a ruptured aorta is very high.

No drugs are currently available to treat aortic aneurysm. But now researchers at Karolinska Institutet and Linköping University have shown that the development of such aneurysms can be slowed in mice with the aid of an existing drug, montelukast. This is commonly used to treat asthma and similar inflammatory diseases of the airways. In a previous study, the researchers had seen that the blood vessel walls of patients with aortic aneurysms often contain abnormally high levels of cysteinyl leukotrienes, which are inflammatory signal substances that cause asthma. These substances can be blocked with montelukast. This led them to investigate whether this anti-asthmatic drug also has an effect on aortic aneurysms.

In the current study, the researchers showed that the treatment reduces the aneurysm formation of the aorta in mice. It also reduces the levels not only of an enzyme that can break down blood vessel walls, MMP-9, but also a protein that is involved in inflammatory processes, MIP-1a. Montelukast had protective effects in three different animal models with different causes of aortic aneurysm. Dick Wågsäter believes that the results show that cellular signalling in which cysteinyl leukotrienes, MMP-9, MIP-1a  and other signal substances interact is important in the disease mechanism, and that it will be interesting to study montelukast in patients with aortic aneurysm.Jesper Z HaeggströmProfessor Jesper Z Haeggström, Karolinska Institutet Photo credit: Anders Wetterholm

"This study is particularly interesting when it comes to treatment options, since montelukast is a safe drug with very few undesired effects. This means that it can be used for long periods. In the study, we used drug doses that corresponded to those used when treating patients with asthma," says Professor Jesper Z. Haeggström of Karolinska Institutet, who led the study.

The research has received financial support from, among others, the Swedish Research Council, the Swedish Heart-Lung Foundation, and Stockholm County Council.

The article: "Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aorta aneurysm", Antonio Di Gennaro, Ana Araujo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z. Haeggström, (2018), Proc Natl Acad Sci, published online on February 5, 2018, doi:10.1073/pnas.1717906115

Previous artikel: "Increased expression of leukotriene C4synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm", Antonio Di Gennaro, Dick Wågsäter, Mikko I. Mäyränpää, Anders Gabrielsen, Jesper Swedenborg, Anders Hamsten, Bengt Samuelsson, Per Eriksson, Jesper Z. Haeggström, (2010), Proc Natl Acad Sci, published online October 19 2010, doi:10.1073/pnas.1015166107

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