Transcriptomic and proteomic profiles of vascular cells involved in human abdominal aortic aneurysm

Abstract

Abdominal aortic aneurysms (AAAs) are a potentially fatal disorder. Atherosclerotic changes followed by accelerated degradation of collagen and elastin, the main components of the extracellular matrix (ECM) in the vascular wall, cause the development of AAAs in deteriorating aortic walls that dilate progressively and may eventually rupture. Other alterations associated with AAAs include marked changes in the cellular composition of the aortic wall, especially the infiltration of macrophages and T-lymphocytes into the adventitia and a major reduction in the population of vascular smooth muscle cells (SMCs) (LopezCandales et al., 1997; Henderson et al., 1999). AAA appear to be a consequence of complex mechanisms involving several potential factors: immunological, inflammatory, chemotactic, apoptotic, protease-related, angiogenic and fibrinolytic (Ailawadi et al., 2003). Recently, interleukin-8 and monocyte chemoattractant protein 1 expression were shown to be raised in the AAA biopsies compared to the abdominal aorta of controls, suggesting that pathways involving these proteins may be involved in AAA pathologies (Middleton et al., 2009). AAA is a disease associated with chronic inflammation in the aortic wall and leukotrienes are powerful lipid mediators released by inflammatory cells (Samuelsson, 1983). A recent study showed the increased expression of leukotriene C4 synthase together with the predominant formation of cysteinyl-leukotrienes in human AAA, linked with matrix metalloproteinases (MMP)