Circumferential heterogeneity in the abdominal aortic aneurysm wall composition suggests lateral sides to be more rupture prone

ObjectiveThe purpose of this study was to identify local differences in inflammation and tissue degradation within the circumference of the abdominal aortic aneurysm (AAA).BackgroundAAAs have the potential to rupture, and it is unknown why this predominantly occurs at the posterolateral wall. Blood flow dynamics likely influence rupture location but do not explain the whole picture, suggesting that other factors inside the AAA wall have a prominent role.MethodsAs part of the Aneurysm-Express study, full thickness circular biopsy specimens of AAAs from 25 patients were obtained during surgery according to a standardized protocol. Tissue from the dorsal, ventral, and lateral sides was processed for histology and protein extraction. Levels of matrix metalloproteinase (MMP)-2 and MMP-9 and various cytokines were measured.ResultsLateral AAA sites, when compared with the ventral and dorsal segments, showed more microvessels (median [interquartile range] per mm2, 91.8 [72.6-124.6] vs 73.9 [63.0-108.0] and 73.6 [52.7-109.5]; P = .013 and P = .005, respectively) and more adventitial inflammation (16.1% [13.5%-24.7%] vs 5.8% [2.8%-18.6%] and 6.3% [4.3%-13.5%]; P = .001 and P < .001, respectively). We observed a higher active MMP-9 (0.139 [0.059-0.339] ng/mL vs 0.060 [0.000-0.157] ng/mL and 0.045 [0.000-0.147] ng/mL; P = .001 and P = .014, respectively) and higher interleukin-8 (28.644 [11.921-62.587] pg/mL vs 16.442 [4.300-34.130] pg/mL and 18.258 [8.273-44.989] pg/mL; P < .001 and P = .010, respectively).ConclusionBiopsy specimens of the ventral AAA wall do not optimally reflect the magnitude of inflammatory processes in the AAA. The lateral sides of the AAA contain more microvessels, more inflammatory cells, more active proteases, and higher cytokine levels. These results suggest that the lateral aortic regions are more rupture-prone and may better reflect the inflammatory status in histopathologic examinations.

Clinical RelevanceAAAs rupture predominantly at the posterolateral wall; however, current tissue research focuses on the ventral wall. This study indicates increased vulnerability of the posterolateral wall, which might better represent the inflammatory status of the wall instead of the current standard. This can be relevant for trials involving pharmaceutical stabilization of the aneurysm by diminishing wall inflammation. In addition, this study feeds the hypothesis that AAA growth might be more pronounced laterally, which is important for the orientation of diameter measurements.