Plasma Levels of Matrix Metalloproteinase-9: A Possible Diagnostic Marker of Successful Endovascular Aneurysm Repair

Hellenthal, F.A.M.V.I.; Bosch, Jan A. Ten; Pulinx, B.; Wodzig, Will K. W. H.; Haan, Michiel W. de; Prins, Martin H.; Welten, R.J.Th.J.; Teijink, Joep A.W.; Schurink, Geert Willem H.

doi:10.1016/j.ejvs.2011.10.014

Cited by 26 publications

(56 citation statements)

References 5 publications

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“…Monaco et al, 25 for example, specifically investigated endoleaks after EVAR for descending thoracic aortic aneurysm compared with AAA in this study, and pathophysiologic differences may complicate direct comparison of their findings and ours. Sample sizes used in this study were larger than those of the previous reports that assessed MMP9 in AAA patients with endoleak, 24,[26][27][28] suggesting greater analytical power, although further studies employing large cohorts of patients are needed to more definitively assess the 20,[29][30][31] attributable in part to the formation of a large nonocclusive thrombus within the aneurysmal sac. 32 Surprisingly, the association of plasma D-dimer concentration with endoleak has been directly examined only in a single study, which reported that circulating D-dimer concentrations were significantly higher in patients suffering type I endoleak (compared with nonendoleak controls) and were highly diagnostic for type I endoleak after ROC analysis.…”

Section: Discussionmentioning

confidence: 94%

“…10 Several prior investigations have assessed the relationship between circulating MMP9 concentrations and endoleak presence, although the significance and extent of the reported associations vary between studies. [24][25][26][27][28] A recent meta-analysis of these studies identified a significant positive association of plasma MMP9 concentration with endoleak presence. 10 The findings of that meta-analysis are contradicted by those of this study as no relationship between endoleak diagnosis and circulating MMP9 concentration was observed.…”

Section: Discussionmentioning

confidence: 99%

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Circulating biomarkers are not associated with endoleaks after endovascular repair of abdominal aortic aneurysms

Moxon

Lazzaroni

et al. 2018

Journal of Vascular Surgery

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Circulating biomarkers are not associated with endoleaks after endovascular repair of abdominal aortic aneurysms

Moxon

Lazzaroni

et al. 2018

Journal of Vascular Surgery

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“…16 In the thoracic aorta, measurement of circulating MMP-9 has been shown to correlate to aortic root dilatation. 17 Interestingly, elevated plasma MMP-9 levels have been used to predict endoleaks after endovascular therapy of the abdominal 18 and thoracic 19 aorta. The present work supports the above results and establishes preliminary algorithms for the screening of patients for ascending aortic aneurysm disease.…”

Section: Discussionmentioning

confidence: 99%

Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease

Ikonomidis

Ivey

Wheeler

et al. 2013

The Journal of Thoracic and Cardiovascular Surgery

105

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Background Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilatation that progresses to rupture if left undetected and untreated. If detected, TAA patients are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging, as no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAV), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). Additionally, altered microRNA (miR) expression levels have also been reported in TAAs as compared to normal aortic tissue. The objective of the present study was to identify circulating factors within the plasma that could serve as potential biomarkers for distinguishing etiological subtypes of aneurysm disease. Methods Ascending TAA tissue and plasma specimens were obtained from BAV (n=21) and TAV (n=21) patients at the time of surgical resection. The protein abundance of key MMPs (-1, -2, -3, -8, -9) and TIMPs (-1, -2, -3, -4), and microRNAs (-1, -21, -29a, -133a, -143, -145) was examined using a multi-analyte protein profiling system or by quantitative PCR, respectively. Results were compared to normal aortic tissue and plasma obtained from patients without aortic disease (n=10). Results Significant (p < 0.05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMPs -1, -3 and -4 (p < 0.05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, -2 and -7, and for decreased MMP-8 and -9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and -9. Conclusions Taken together these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized medicine strategies to distinguish between etiological subtypes of TAAs in patients with aneurysm disease.

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“…Among EVAR patients, those with endoleak have significantly higher levels of plasma MMP-9 levels than those without endoleak (89.54 ± 26.46 vs 25.02 ± 13.40 ng/ml; p < 0.001). Regression analysis showed no significant influence of age, sex and AAA sizes [87]. In a population-based study from the Dallas Heart Study, higher plasma MMP-9 levels independently associated with higher aortic wall thickness (p < 0.0001) and larger luminal diameter (p < 0.0001) [88].…”

Section: Association Of Circulating Mmps With Human Aaasmentioning

confidence: 99%

Cysteine Protease Cathepsins and Matrix Metalloproteinases in the Development of Abdominal Aortic Aneurysms

et al. 2012

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Both cysteine protease cathepsins and matrix metalloproteinases are implicated in the pathogenesis of abdominal aortic aneurysms (AAAs) in humans and animals. Blood and aortic tissues from humans or animals with AAAs contain much higher levels of these proteases, and often lower levels of their endogenous inhibitors, than do blood and aortic tissues from healthy subjects. Protease- and protease inhibitor-deficient mice and synthetic protease inhibitors have affirmed that cysteinyl cathepsins and matrix metalloproteinases both participate directly in AAA development in several experimental model systems. Here, we summarize our current understanding of how proteases contribute to the pathogenesis of AAA, and discuss whether proteases or their inhibitors may serve as diagnostic biomarkers or potential therapeutic targets for this common human arterial disease.

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Plasma Levels of Matrix Metalloproteinase-9: A Possible Diagnostic Marker of Successful Endovascular Aneurysm Repair

Abstract: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

Cited by 26 publications

References 5 publications

Circulating biomarkers are not associated with endoleaks after endovascular repair of abdominal aortic aneurysms

Circulating biomarkers are not associated with endoleaks after endovascular repair of abdominal aortic aneurysms

Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease

Cysteine Protease Cathepsins and Matrix Metalloproteinases in the Development of Abdominal Aortic Aneurysms

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