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Mouse gene shows new mechanism behind cardiac infarction in man

11 Mar 2005 - A gene that, in different variants, increases or decreases the level of atherosclerosis has been identified in mice. The corresponding human gene has been shown to play a role in the development of myocardial infarction. Researchers at Karolinska Institutet, in collaboration with the Jackson Laboratory in the USA, AstraZeneca and a Japanese research group, have scrutinised an area on chromosome 1 that is of demonstrable importance to the development of arteriosclerosis. The TNFSF4 gene was identified as the one responsible, as mice with mutations in this gene displayed a lower degree of atherosclerosis, while mice with more active variants of the gene displayed the opposite.
 
Studies of two patient groups revealed that a certain variant of the human homologue of the gene was more common in people who had a history of cardiac infarction than those without.
 
"This is an example of how an unbiased genetic strategy based on a mice model can teach us more about common human diseases," says researcher Jacob Lagercrantz of the Gustav V research institute, Karolinska Institutet.
 
The gene codes for a protein called OX40L, which is involved in the activation of immunological T cells. These cells, in turn, play an important role in the pathogenesis of atherosclerosis and of a number of chronic inflammatory diseases. The new finding will spur further research into the relationship between the protein and cardiac infarction. Hopefully it will offer a new therapeutic technique for the treatment of atherosclerosis and thus reduce the risk of cardiac infarction.
 
Publication: X. Wang, M. Ria, P.M. Kelmenson, P. Eriksson, D.C. Higgins, A. Samnegård, C. Petros, J. Rollins, A.M. Bennet, B. Wiman, U. De Faire, C. Wennberg, P.G. Olsson, N. Ishii, K. Sugamura, A. Hamsten, K. Forsman-Semb, J. Lagercrantz, B. Paigen; "Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility."; Nature Genetics Online 2005.