The formation of thoracic aortic aneurysms (TAA) is a multifactorial process influenced by both cellular and extracellular mechanisms. These mechanisms lead to alterations in the vascular environment through remodeling of the extracellular matrix (ECM); an invariant feature directly implicated in aortic dilatation and aneurysm development. TAAs have numerous etiologies and recent data suggests that dissimilarities exist between TAA subtypes, specifically in regard to the proteolytic balance within the aortic wall. This is most notable for the matrix metalloproteinases. While the role of enhanced ECM proteolysis in TAA formation remains undisputed, the fundamental signaling mechanisms regulating the perturbations in matrix deposition and degradation in the developing aneurysm are not well understood.
My research interests are focused on identifying upstream signaling pathways and mediators that drive the dynamic changes in the production and secretion of extracellular matrix components during aneurysm formation. These mechanisms include: 1) signaling pathways involving transforming growth factor-β (TGF-β), 2) alterations in the cellular composition within the vascular wall that occur during TAA development, and 3) the role of intracellular signaling mediators such as protein kinase C (PKC) in mediating the balance between ECM degradation and deposition. Our primary goal is to advance the understanding of the basic mechanisms driving TAA formation, and to develop strategies for arresting TAA development or even reversing TAA progression.
Jones JA, Stroud RE, Kaplan BS, Leone AM, Bavaria JE, Gorman JH 3rd, Gorman RC, Ikonomidis JS. Differential protein kinase C isoform abundance in ascending aortic aneurysms from patients with bicuspid versus tricuspid aortic valves. Circulation. 2007 Sep 11;116(11 Suppl):I144-9.
Jones JA, Barbour JR, Stroud RE, Bouges S, Stephens SL, Spinale FG, Ikonomidis JS. Altered Transforming Growth Factor-Beta Signaling in a Murine Model of Thoracic Aortic Aneurysm. J Vasc Res. 2008 Apr 23;45(6):457-468.
Jones JA, Spinale FG, Ikonomidis JS. Transforming Growth Factor-beta Signaling in Thoracic Aortic Aneurysm Development: A Paradox in Pathogenesis. J Vasc Res. 2008 Sep 2;46(2):119-137.