Increased matrix metalloproteinase 9 activity correlates with flow-mediated intraluminal thrombus deposition and wall degeneration in human abdominal aortic aneurysm

Abstract

Objective We have previously demonstrated that human abdominal aortic aneurysm (AAA) rupture occurs in zones of low wall shear stress where flow recirculation and intraluminal thrombus (ILT) deposition are increased. Matrix metalloproteinase-9 (MMP-9) is involved in the pathogenesis of AAA via its lytic effect on collagen and elastin. We hypothesize that flow-mediated ILT deposition promotes increased local inflammatory and MMP-9 activity that leads to AAA wall degeneration. The purpose of this study was to examine the correlation between predicted pulsatile flow dynamics and regional differences in MMP-9, elastin, collagen, and ILT deposition in human AAA. Methods Full-thickness aortic tissue samples were collected from 24 patients undergoing open AAA repair. Control infrarenal aortic tissue was obtained from 6 patients undergoing aortobifemoral bypass. Full-thickness aortic tissue and ILT were assessed for MMP-9 levels using a cytokine array assay. Histologic and immunohistochemical assessment of inflammation, collagen and elastin content, and MMP-9 levels were also measured. Three-dimensional AAA geometry was generated from computed tomography angiogram (CTA) images using Mimics software and computational fluid dynamics was used to predict pulsatile aortic blood flow. Results The majority of AAA showed eccentric ILT deposition which was correlated with predicted recirculation blood flow (R 2 = –0.17; P < .05). The regions of high ILT were associated with significant increases in inflammation and loss of elastin and collagen compared with regions of low ILT, or with control tissue. MMP-9 was significantly higher in areas of high ILT deposition compared with areas devoid of ILT. Tissue MMP-9 was correlated with the thickness of ILT deposition (R 2 = 0.46; P < .05), and was also present in high levels in thick compared with thin ILT. Conclusions We have shown a correlation between flow-mediated ILT deposition with increased tissue levels of MMP-9 activity, increased inflammatory infiltrate, and decreased elastin and collagen content in stereotactically sampled human AAA, suggesting that ILT deposition is associated with local increases in proteolytic activity that may preferentially weaken and promote rupture at selected regions.

Intraluminal thrombus: Innocent bystander or factor in abdominal aortic aneurysm pathogenesis?

“…In contrast, when full-thickness human aortic tissues samples were stereographically biopsied over the entire aorta from patients undergoing open AAA repair and correlated with computationally derived hemodynamics, high MMP-9 levels correlated positively low WSS and high ILT deposition, increased inflammatory infiltrate, and decreased elastin and collagen content. 123 …”

“… 122 In contrast, in the latter study, biopsies were taken from a representative section of the entire aorta and mainly compared the ILT and no-ILT regions. 123 In addition, thin ILT might have been recently deposited and, thus, might have had greater inflammatory activity, similar to that seen in the luminal layer of discrete ILT. Samples of thick ILT likely had deeper, more inert, layers included in the sample, which might have diluted the measurements of the inflammatory markers.…”

On growth, buckling, and rupture of aneurysms

“…It is not clear whether the buckling always follows the bulge or vice versa. However, many AAAs are commonly observed in a buckled state (Fillinger et al, 2004;Ducas et al, 2020;Hejazi et al, 2021) do not rupture at a much larger size (Choi et al, 2021). This study suggests that a straight aneurysm has a higher risk of rupture compared to a buckled aneurysm.…”

“…However, some AAAs are found unruptured despite their maximum size exceeding the minimum recommended size (5.5 cm) for surgical interventions (Lazaris, 2019;Fillinger et al, 2004). Tortuous and buckled AAAs whose size far exceed the guidelines have been observed without rupture (Fillinger et al, 2004;Hejazi et al, 2021;Boyd et al, 2016;Ducas et al, 2020;Choi et al, 2021). Arterial stability with aneurysm (Lee et al, 2014) and buckling without aneurysms (Liu et al, 2019) has also been studied, among others.…”

Great start predicts bright future for JVS-Vascular Science

“…JVS-VS , the official publication of the Society for Vascular Surgery (SVS) is the fourth member of the JVS portfolio ( Table ). 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 2021 has been a year of growth and transformation for all the journals of the JVS family. The Journal of Vascular Surgery (JVS) earned an all-time-high impact factor of 4.268, the Journal of Vascular Surgery: Venous and Lymphatic Disorders (JVS-VL) reinforced its position as the leading publication in the international venous and lymphatic field with an impact factor of 2.859, and the Journal of Vascular Surgery Cases, Innovations and Techniques substantially increased the content and number of its open access, on-line publications.…”