Difference in Matrix-Degrading Protease Expression and Activity Between Thrombus-Free and Thrombus-Covered Wall of Abdominal Aortic Aneurysm

Kazi, Monsur; Zhu, Changliang; Roy, Joy; Paulsson-Berne, Gabrielle; Hamsten, Anders; Swedenborg, Jesper; Hedin, Ulf; Eriksson, Per

doi:10.1161/01.atv.0000166601.49954.21

Cited by 78 publications

(67 citation statements)

References 36 publications

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“…The role of the thrombus in aneurysm expansion and rupture is uncertain. 30,32,33 Some macrophages are present deep within the thrombus, but, alternatively, this signal pattern may reflect USPIO within the canaliculi that traverse the thrombus, conducting fluid, small molecules and, to a certain extent, cells from the lumen toward the aortic wall. 30 This pattern of USPIO uptake and inflammation within the thrombus is of uncertain significance but interestingly did not appear to be associated with accelerated aneurysm growth.…”

Section: Discussionmentioning

confidence: 99%

Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide

Richards

Semple²,

MacGillivray³

et al. 2011

Circ: Cardiovascular Imaging

160

164

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Background-Abdominal aortic aneurysms are a major cause of death. Prediction of aneurysm expansion and rupture is challenging and currently relies on the simple measure of aneurysm diameter. Using MRI, we aimed to assess whether areas of cellular inflammation correlated with the rate of abdominal aortic aneurysm expansion. Methods and Results-Stable patients (nϭ29; 27 male; age, 70Ϯ5 years) with asymptomatic abdominal aortic aneurysms (4.0 to 6.6 cm) were recruited from a surveillance program and imaged using a 3-T MRI scanner before and 24 to 36 hours after administration of ultrasmall superparamagnetic particles of iron oxide (USPIO). The change in T2* value on T2*-weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. Histological examination of aneurysm tissue confirmed colocalization and uptake of USPIO in areas with macrophage infiltration. Patients with distinct mural uptake of USPIO had a 3-fold higher growth rate (nϭ11, 0.66 cm/y; Pϭ0.020) than those with no (nϭ6, 0.22 cm/y) or nonspecific USPIO uptake (nϭ8, 0.24 cm/y) despite having similar aneurysm diameters (5.4Ϯ0.6, 5.1Ϯ0.5, and 5.0Ϯ0.5 cm, respectively; PϾ0.05). In 1 patient with an inflammatory aneurysm, there was a strong and widespread uptake of USPIO extending beyond the aortic wall. Conclusions-Uptake of USPIO in abdominal aortic aneurysms identifies cellular inflammation and appears to distinguish those patients with more rapidly progressive abdominal aortic aneurysm expansion.

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Section: Discussionmentioning

confidence: 99%

Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide

Richards

Semple²,

MacGillivray³

et al. 2011

Circ: Cardiovascular Imaging

160

164

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“…14) Kazi, et al also demonstrated that upregulation of MMPs was found in the aneurysm wall without thrombus. 15) Our data indicate that the relationship between ILT of AAA and MMPs may be associated with AAA sac shrinkage after EVAR. Cornelissen, et al reported that recent use of magnetic resonance imaging (MRI) in some cases, as a method of evaluating the size of aneurysm sac after EVAR, revealed that half of the non-shrinking aneurysm sac contents consisted of unorganized thrombus several years after EVAR.…”

Section: Discussionmentioning

confidence: 59%

Factors for Sac Size Change of Abdominal Aortic Aneurysm after Endovascular Repair

Tsuyuki

Matsushita

Dohi

et al. 2014

ATCS

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Objectives: Factor(s) affecting the sac size of an abdominal aortic aneurysm (AAA) after endovascular aneurysm repair (EVAR) remain unclear. We compared the diameter of the aneurysm sac at one year after surgery with the preoperative diameter using CT images. Methods: Patients who underwent EVAR at Juntendo University Hospital were involved. According to the size change in treated lesions of the aorta, patients were categorized into the following 3 groups: shrink (<5 mm of reduction), enlarge (>5 mm of expansion), and no change (size change within 5 mm). The patients' background, laboratory data, devices used, medications, anatomical characteristics, and presence/absence of postoperative endoleaks were examined. Results: Of the 68 consecutive patients, 23 were excluded. Seventeen patients were classified into the shrink group, 28 patients into the no change group, and no patients into the enlarge group. Patients with higher thrombotic area rate on the preoperative AAA tended to present AAA sac shrinkage (p = 0.05). No other variables affected the size change in this study. In addition, the existence of an endoleak suggested the interference of sac shrinkage. Conclusions: The higher AAA thrombotic area rate tended to associate with AAA sac shrinkage.

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“…Production of MMPs by macrophages under these conditions are believed to be implicated in weakening of arterial walls (Vorp, et al, 2001) (Kazi, et al, 2005) (Murdoch, et al, 2005) (Oya, et al, 2011). In the present study, we focused on the effect of oxygen concentrations on MMP production of macrophages subjected to cyclic stretching.…”

Section: Discussionmentioning

confidence: 99%

“…Studies for AAA tissues have found extensive inflammatory infiltrates such as macrophages and T lymphocytes (Bobryshev, et al, 1998) (Pearce and Koch, 1996), and increased expression of MMPs (Thompson, et al, 1995), which is a family of enzymes that proteolytically degrade various components of the extracellular matrix. Since MMP-9, the most abundant gelatinolytic MMP and secreted in high levels in AAA tissue (Thompson, et al, 1995), colocalized with infiltrated macrophages (Kazi, et al, 2005), functions of macrophages under AAA walls conditions have been examined in association of formation and enlargement of aneurysms.…”

Section: Introductionmentioning

confidence: 99%

Effect of low oxygen conditions on matrix metalloproteinase-9 production of macrophages subjected to cyclic stretching: involvement of ERK and Rho kinase pathways

Sakamoto

Sadamoto

2017

JBSE

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Macrophages infiltrated in the walls of abdominal aortic aneurysms (AAA) are subjected to cyclic stretching due to pulsatile deformation of blood vessels and low oxygen conditions caused by intraluminal thrombus. These conditions could induce aberrant changes in macrophage functions and lead local weakening of AAA walls. We previously reported that the combination of 10 % cyclic stretching and 2.2% O 2 conditions caused an increase in matrix metalloproteinase-9 (MMP-9) production in macrophages as well as changes in morphological responses to cyclic stretching. In the present study, we investigated the effects of oxygen concentrations on MMP-9 productions and morphological changes of macrophages subjected to cyclic stretching. Macrophages differentiated from THP-1 cells were subjected to 10% cyclic stretching under 5% or 1% O 2 conditions for 24 h, and gelatinolytic activity of MMP-9 in the conditioned medium was assessed by zymography. Cells showed spread and rounded shape under static conditions and elongated and oriented to the direction of stretching after exposure to cyclic stretching, and there were no obvious effects of oxygen concentrations in cell morphology. An O 2 concentration of 5% did not change MMP-9 productions of macrophages in static culture and subjected to cyclic stretching compared to normal cell culture condition of 20% O 2 . In contrast, 1% O 2 condition stimulated MMP-9 production of macrophages both under static culture and cyclic stretching conditions. We also found that treatments of inhibitors for extracellular signal-regulated kinase (ERK) and Rho associated protein kinase (Rho kinase) suppressed the increased MMP-9 productions of macrophages by 1% O 2 condition. These results suggest that lower oxygen conditions such as 1% O 2 stimulate MMP-9 production in macrophages through signaling pathways involving ERK as well as Rho kinase-mediated actin cytoskeletal contractility.

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Difference in Matrix-Degrading Protease Expression and Activity Between Thrombus-Free and Thrombus-Covered Wall of Abdominal Aortic Aneurysm

Abstract: The present work demonstrates that protease expression and activity differs within the aneurysm wall. The source and activity of the proteases responsible for the degradation of the thrombus-covered wall need to be further determined.

Cited by 78 publications

References 36 publications

Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide

Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide

Factors for Sac Size Change of Abdominal Aortic Aneurysm after Endovascular Repair

Effect of low oxygen conditions on matrix metalloproteinase-9 production of macrophages subjected to cyclic stretching: involvement of ERK and Rho kinase pathways

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