Abdominal Aortic Aneurysm as a Complex Multifactorial Disease

Abstract

The role of matrix metalloproteinases (MMPs) in the pathogenesis of abdominal aortic aneurysm (AAA) has focused on the degradation of the extracellular matrix (ECM). The new frontier of MMP biology involves the role of MMPs in releasing cryptic fragments and neoepitopes from the ECM and the impact of MMPs on the regulation of the inflammatory response. The ECM is a complex structure, much more important than an inert scaffold. Both MMP-2 and MMP-9 expose a cryptic epitope that controls angiogenesis. MMPs inhibit angiogenesis through the release of endostatin, endorepellin, arresten, canstatin, and tumstatin. Other breakdown products of the ECM include fragments of fragmin and elastin degradation products (EDPs). In addition, the ECM contains embedded vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta). Inflammation is a complex, highly regulated system that involves the identification of injury or infection, response to the injury or infection, repair and healing, and return to normal homeostasis. In some instances, the inflammatory process leads to a pathologic process that is damaging to the host. MMPs play an important role in the control of the inflammatory response through the modification of proinflammatory cytokines, chemokines, and shedding of membrane receptors. Genetic association studies have been performed to help determine the genetic risk associated with certain single nucleotide polymorphisms (SNPs) However, because of the variability in the patient populations and the size of the population, it is difficult to draw any conclusions from these studies. While the etiology of AAA remains unknown, understanding of the inflammatory process and its regulatory points will develop new strategies for the treatment of AAA. Perhaps one difficulty with understanding the pathogenesis of AAA is the lack of precise definition of the phenotype.

A finite element model of stress-mediated vascular adaptation: application to abdominal aortic aneurysms

“…Although we used simple spatial and temporal functions for elastin degradation, elastin degradation during AAA growth involves multiple biological and mechanical parameters. It has been suggested that in AAAs, elastin degradation is due to the proteolytic activity which may have several causes including abnormal distribution of wall shear stress (Miller 2002;Hoshina et al 2003;Sho et al 2004), circumferential stress , influx of inflammatory cells (Choke et al 2005;Pearce and Shively 2006;Shimizu et al 2006;Middleton et al 2007) and the formation of the intraluminal thrombus layer (Vorp et al 2001;Fontaine et al 2002;Vorp and Vande Geest 2005). In our following study (Sheidaei et al 2010), the current model is coupled with haemodynamic simulation in an iterative manner, and the effects of wall shear stress on the elastin degradation and, hence, on the aneurysm growth are investigated.…”

Degenerative disease in rotator cuff tears: what are the biochemical and histological changes?

“…These results indicate that tendon tissue cells are capable of producing a remodeling response even in end-stage tendon disease (9). Recent studies suggest that MMPs could play a role in the inflammatory process through cytokines such as IL 1,4,6, and 10, TNF, and GF, which can increase the synthesis and release of neoepitopes from the ECM (19). Inflammatory cytokines are involved in pain and tendon healing.…”

Elevated MMP‐8 and Decreased Myeloperoxidase Concentrations Associate Significantly with the Risk for Peripheral Atherosclerosis Disease and Abdominal Aortic Aneurysm1

“…Series of inflammatory reactions as measured by increased serum inflammatory markers have been shown to be associated with atherosclerosis, carotid artery stenosis, and AAA [12][13][14]. The role of MMPs and their regulators in arterial disease remains; despite several existing publications, unclear, and the balance between MMPs and their regulators requires further investigation.…”