Biomechanics and gene expression in abdominal aortic aneurysm

Abstract

Our results show for the first time that gene expressions of destabilizing factors within AAA tissue might be correlated to geometric and mechanical properties of the AAA wall. However, we found no influence of local mechanical conditions on gene expression of these factors. Therefore, these preliminary results are still ambiguous.

Gene Expression Profiling in Abdominal Aortic Aneurysms After Finite Element Rupture Risk Assessment

“…Reeps et al 3 concluded from destructive testing that expression of AAA candidate genes, including inflammatory factors (CD45, MSR1), proteolytic enzymes (MMP2, MMP9, TIMP-1) and collagen types I and III, are associated with geometrical and mechanical properties. However, a relation between local calculated AAA wall stress from FEA and regional gene expression could not be found.…”

“…However, the interaction between local genomic expression patterns and biomechanical conditions contributing to wall weakening effects, a phenomenon recently referred to as “mechanotransduction,” is poorly understood. Reeps et al 3 postulated that gene expression of destabilizing factors might be associated with focal geometrical and mechanical properties of the AAA wall. However, calculated wall stress patterns from FEA were not related to local differences in gene expressions.…”

Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume

“…On the protein/structural/cellular level, high ratio between wall stress and wall strength was associated with decreased vSMCs and elastic fibers as well as more cholesterol and calcified plaques, whereas increased wall stress was associated with increased collagen 1, III and total collagen (283). With respect to local tissue mechanics, stiffness and strength of the AAA vessel wall correlate negatively with MMP2 gene expression (282). Finally, mechanical stretching of vSMCs cause oxidative stress and makes them pro-inflammatory, -fibrotic and -proteolytic (284-286).…”

“…An intriguing concept of biomechanical-biological interactions in AAA was that of segmental aortic stiffening increasing the axial tensile stress in adjacent, compliant, segments causing increased inflammation and proteolysis, which also correlated with age-related changes in the human aorta (281). Investigations into associations between gene expression and wall stress or the estimated ratio between wall stress and wall strength have pointed to differences in expression of lamin A/C and genes related to ECM and cytokine signaling, while strong associations surviving correction for multiple testing are difficult to obtain (228,229,282). On the protein/structural/cellular level, high ratio between wall stress and wall strength was associated with decreased vSMCs and elastic fibers as well as more cholesterol and calcified plaques, whereas increased wall stress was associated with increased collagen 1, III and total collagen (283).…”

Baroreceptors in the Aortic Arch and Their Potential Role in Aortic Dissection and Aneurysms

“…Aortic aneurysm (AA) is a life-threatening clinical condition, characterized as a pathological expansion of the aorta, particularly in an elderly population (>65 years) [ 79 , 80 , 81 , 82 , 83 ]. Proteolytic degradation of the extracellular matrix (ECM) is thereby the main factor weakening the aortic wall, leading to diameter expansion and finally to rupture [ 81 , 82 ].…”