Preventing and Treating Aortic Aneurysms

The cause of an aortic aneurysm remains poorly understood and successful pharmacotherapy is lacking despite the role of aneurysms as a major source of morbidity and death. Unregulated inflammatory and tissue repair processes underlie the maladaptive response of the vascular wall that leads to aneurysm formation.

AAA_1   AAA_2   AAA_3

Thus, there is great motivation for understanding the interplay between the complex biochemical, cellular, and biomechanical phenomena, which control inflammation and tissue repair in the vascular wall. We postulate that expression and shedding of the heparan sulfate proteoglycan syndecan-1 may provide an importantmechanism that inhibits abdominal aortic aneurysm (AAA) formation by limiting proteolytic or inflammatory activity and by promoting local reparative responses. The experimental approach within this project area is designed to yield fundamental knowledge regarding the regulated expression and shedding of syndecan-1, which we believe is an important molecular determinant modulating inflammatory and tissue repair processes in the vascular wall.

Li L, Chaikof EL. Mechanical stress regulates syndecan-4 expression and redistribution in vascular smooth muscle cells. Arteriosclerosis Thromb Vasc Biol 2002; 22:61-68.

Houston M, Julien MA, Parthasarathy S, Chaikof EL. Oxidized linoleic acid regulates expression and shedding of syndecan 4. Am J Physiol – Cell Physiol. 2005; 288:C458-66.

Julien MA, Haller CA, Wang P, Wen J, Chaikof EL. Mechanical strain induces a persistent upregulation of syndecan-1 expression in smooth muscle cells. J Cell Physiology 2007; 211:167-173.

Xiao J, Angsana J, Wen J, Smith SV, Park PW, Ford ML, Haller CA, Chaikof EL. Syndecan-1 displays a protective role in aortic aneurysm formation by modulating T cell-mediated responses. Arteriosclerosis Thromb Vasc Biol 2012; 32:386-96.