Elevated Plasma Levels of Matrix Metalloproteinase-9 in Patients with Abdominal Aortic Aneurysms: A Circulating Marker of Degenerative Aneurysm Disease

Hovsepian, David M.; Ziporin, Scott J.; Sakurai, Maromi K.; Lee, Jason K.; Curci, John A.; Thompson, Robert W.

doi:10.1016/s1051-0443(07)61315-3

Cited by 134 publications

(112 citation statements)

References 26 publications

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“…Failure to regulate these functions can be detrimental. For example, pro-MMP-9, as well as active MMP-9, levels are significantly elevated among patients with abdominal aortic aneurysms (5,12,18,23,24). Since the clinical presentation of KD involves vasculitis and coronary aneurysm, we posited that MMP-9 enzyme and protein levels are elevated in KD patients.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Chua

Melish

et al. 2003

Clin Vaccine Immunol

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Kawasaki disease (KD) is an acute, self-limiting, multisystem vasculitis of unknown etiology affecting infants and young children. Unless treated promptly with high-dose intravenous gamma globulin and aspirin, patients frequently develop coronary aneurysms. Previously, matrix metalloproteinase 9 (MMP-9), which is secreted complexed to tissue inhibitor of metalloproteinase 1 (TIMP-1), has been implicated in abdominal aortic aneurysm formation. Since the clinical and pathological features of KD include inflammation and weakening of blood vessels, we analyzed acute-and convalescent-phase paired plasma or serum samples from 31 KD patients, 7 patients who did not completely meet the criteria for KD, and 26 non-KD controls (9 febrile and 17 afebrile patients) for pro-MMP-9 (92 kDa) enzyme activity by gelatin zymography and for active MMP-9 (83 kDa), pro-MMP-9, and TIMP-1 protein levels by enzyme-linked immunosorbent assay. Statistical analysis was performed by using Student t tests, linear regression, and the Wilcoxon rank-sum test. Markedly elevated pro-MMP-9 enzymatic activity, pro-MMP-9 protein levels, and TIMP-1 protein levels were found during the acute phase of illness in patients with clinically established KD and in patients who were suspected of having KD but did not meet all of the criteria. There was no significant difference in active MMP-9 levels. Furthermore, pro-MMP-9 and TIMP-1 protein levels were significantly elevated among KD patients, compared to those of febrile and afebrile non-KD controls. The significantly elevated pro-MMP-9 enzyme and protein levels during the acute phase of KD may reflect vascular remodeling or an inflammatory response to a microbial agent, suggesting a pathophysiological role for MMP-9 in coronary aneurysm formation.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Chua

Melish

et al. 2003

Clin Vaccine Immunol

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“…2,16,17 Recently, Hovsepian and associates 45 have reported a significant decrease in plasma levels of MMP-9 after surgical exclusion of AAA, suggesting that circulating MMP-9 may provide a biologically relevant marker of successful aneurysm repair. The present study is in agreement with the results, demonstrating that either after OSR or endovascular exclusion by stent graft placement, MMP-9 and MMP-3 decrease similarly during follow-up.…”

Section: Mmps Aaas and Surgical Treatmentmentioning

confidence: 99%

Plasma Levels of Metalloproteinases-3 and -9 as Markers of Successful Abdominal Aortic Aneurysm Exclusion After Endovascular Graft Treatment

et al. 2001

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A spiral CT scan was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels were measured before EVG (nϭ30) and OSR (nϭ15) treatments and at 1, 3, and 6 months of follow-up by a sandwich ELISA technique. Healthy volunteers (nϭ10) were used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal levels were significantly higher in patients affected by AAA than in control subjects (32.3Ϯ20.7 ng/mL for EVG and 28Ϯ9.9 ng/mL for OSR versus 8.9Ϯ2.5 ng/mL, 2PϽ0.05; 18.3Ϯ9.7 ng/mL and 26.7Ϯ10.8 ng/mL versus 8.2Ϯ5.3 ng/mL, 2PϽ0.001).In the OSR group, both MMP-9 and MMP-3 mean levels decreased after surgery (28Ϯ9.9 ng/mL at basal versus 14.7Ϯ6.6 ng/mL at 6 months, 2PϽ0.001; 26.7Ϯ10.8 versus 12Ϯ5.3 ng/mL; 2PϽ0.001). In the EVG group, a statistically significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values was detected in patients who had endoleakage in comparison with patients without endoleakage (44.3Ϯ20.7 versus 14.6Ϯ7.0 ng/mL, 2PϽ0.005; 25Ϯ11.5 versus 10.3Ϯ5.4 ng/mL, 2PϽ0.005). Conclusions-After EVG exclusion, MMP-9 and MMP-3 levels decreased to a level similar to that of patients undergoing OSR. In addition, a lack of decrease in MMP levels after EVG exclusion may help in identifying patients who will have endoleakage and consequent aneurysm expansion caused by continuous sac pressurization during follow-up.

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“…MMP-9 plasma concentrations in patients with AAAs appeared to directly reflect the amount of MMP-9 released within aneurysm tissue. Serum MMP-9 concentration has been shown to fall significantly after AAA repair [9,10]. The first study reporting the prognostic value of MMP-9 in AAA therapy was published by Sangiorgi et al [11].…”

Section: Introductionmentioning

confidence: 99%

MMP-9, Homocysteine and CRP Circulating Levels Are Associated with Intraluminal Thrombus Thickness of Abdominal Aortic Aneurysms–New Implication of the Old Biomarkers

et al. 2011

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Abstract. Background: Abdominal aortic aneurysms (AAAs) are characterized by presence of high proteolytic activity, atherosclerotic lesions, extensive transmural inflammation and the presence of variably sized and shaped intraluminal thrombus (ILT). Therefore, we evaluated a possible association between plasma matrix metalloproteinase-9 (MMP-9), homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP) levels and ILT thickness in patients with AAA. Methods: Plasma concentrations of MMP-9, Hcy and hsCRP were determined and ILT thickness was measured in 71 patients with AAA. They were divided into 2 groups according to ILT thickness: 34 patients with ILT mean thickness 9 mm and 37 patients with ILT < 9 mm. Results: Plasma MMP-9 and CRP concentrations in patients with thin ILT were significantly higher than in group with thick ILT (medians 610 vs. 485 ng/mL, p = 0.00003, and 7.7 vs. 3.3 mg/L, p < 0.00001, respectively). In contrast, plasma Hcy concentrations in patients with thin ILT were significantly lower than in the group with thick ILT (medians 14.3 vs. 19.2 µmol/L, p < 0.00001). Multiple regression models adjusted for age and AAA diameter showed that thin ILT is an independent predictor of high MMP-9 and CRP concentrations, while thick ILT predicts high Hcy concentrations. Conclusions: Association of higher plasma levels of MMP-9 and CRP with thin ILT may be related to two phenomena: thin thrombi convey more elastolysis-stimulating factors from blood to the AAA wall and thin thrombi convey more factors involved in proteolysis and inflammation from AAA wall to blood. The association of thin ILT with lower plasma Hcy concentrations may be related to the role of Hcy as a prothrombotic marker and needs further research.

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Elevated Plasma Levels of Matrix Metalloproteinase-9 in Patients with Abdominal Aortic Aneurysms: A Circulating Marker of Degenerative Aneurysm Disease

Cited by 134 publications

References 26 publications

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Elevated Levels of Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 during the Acute Phase of Kawasaki Disease

Plasma Levels of Metalloproteinases-3 and -9 as Markers of Successful Abdominal Aortic Aneurysm Exclusion After Endovascular Graft Treatment

MMP-9, Homocysteine and CRP Circulating Levels Are Associated with Intraluminal Thrombus Thickness of Abdominal Aortic Aneurysms–New Implication of the Old Biomarkers

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