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      KCI등재후보 SCIE SCOPUS

      Plaque Rupture is a Determinant of Vascular Events in Carotid Artery Atherosclerotic Disease: Involvement of Matrix Metalloproteinases 2 and 9

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      https://www.riss.kr/link?id=A101598325

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      다국어 초록 (Multilingual Abstract)

      Background and Purpose: Unstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. T...

      Background and Purpose: Unstable carotid atherosclerotic plaques are characterized by cap rupture, leading to thromboembolism and stroke. Matrix metalloproteinases (MMPs) have been implicated in the progression of atherosclerosis and plaque rupture. The aim of this study was to assess the relationship between the expressions of MMP-2 and MMP-9 and carotid plaque instability.
      Methods: Eighty atherosclerotic plaques were collected from 74 patients undergoing carotid endarterectomy. Clinical information was obtained from each patient, and plaque morphology was examined at the macroscopic and microscopic levels. The immunohistochemical expressions of MMPs were graded using semiquantitative scales.
      Results: Macroscopic ulceration (84.6% versus 63.4%, p=0.042) and microscopic cap rupture (79.5% versus 51.2%, p=0.010) were more common in symptomatic than in asymptomatic patients.
      Immunoreactivities of MMP-2 and MMP-9 were increased in 40 and 36 atheromatous plaques,respectively. Macroscopic ulceration was strongly correlated with the expressions of MMP-2(p<0.001) and MMP-9 (p=0.001). There were significant correlations between increased MMP2 expression and cap rupture (p=0.002), intraplaque hemorrhage (p=0.039), and a thin fibrous cap (p=0.002), and between increased MMP-9 expression and cap rupture (p=0.010) and a large lipid core (p=0.013).
      Conclusions: Plaque rupture was significantly associated with the development of vascular events in carotid atherosclerotic disease. MMP-2 and MMP-9 are strongly correlated with plaque instability.

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      참고문헌 (Reference)

      1 Hachinski V, 39 : 1067-, 2008

      2 Kagawa R, "Validity of B-mode ultrasonographic findings in patients undergoing carotid endarterectomy in comparison with angiographic and clinicopathologic features" 27 : 700-705, 1996

      3 Molloy KJ, "Unstable carotid plaques exhibit raised matrix metalloproteinase- 8 activity" 110 : 337-343, 2004

      4 Galis ZS, "Thrombin promotes activation of matrix metalloproteinase-2 produced by cultured vascular smooth muscle cells" 17 : 483-489, 1997

      5 Alvarez B, "Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis" 40 : 469-475, 2004

      6 Lovett JK, "Reproducibility of histological assessment of carotid plaque: implications for studies of carotid imaging" 18 : 117-123, 2004

      7 Stary HC, "Natural history and histological classification of atherosclerotic lesions: an update" 20 : 1177-1178, 2000

      8 Shah PK, "Mechanisms of plaque vulnerability and rupture" 41 : 15-22, 2003

      9 Kähäri VM, "Matrix metalloproteinases in skin" 6 : 199-213, 1997

      10 Loftus IM, "Matrix metalloproteinases and atherosclerotic plaque instability" 89 : 680-694, 2002

      1 Hachinski V, 39 : 1067-, 2008

      2 Kagawa R, "Validity of B-mode ultrasonographic findings in patients undergoing carotid endarterectomy in comparison with angiographic and clinicopathologic features" 27 : 700-705, 1996

      3 Molloy KJ, "Unstable carotid plaques exhibit raised matrix metalloproteinase- 8 activity" 110 : 337-343, 2004

      4 Galis ZS, "Thrombin promotes activation of matrix metalloproteinase-2 produced by cultured vascular smooth muscle cells" 17 : 483-489, 1997

      5 Alvarez B, "Serum values of metalloproteinase-2 and metalloproteinase-9 as related to unstable plaque and inflammatory cells in patients with greater than 70% carotid artery stenosis" 40 : 469-475, 2004

      6 Lovett JK, "Reproducibility of histological assessment of carotid plaque: implications for studies of carotid imaging" 18 : 117-123, 2004

      7 Stary HC, "Natural history and histological classification of atherosclerotic lesions: an update" 20 : 1177-1178, 2000

      8 Shah PK, "Mechanisms of plaque vulnerability and rupture" 41 : 15-22, 2003

      9 Kähäri VM, "Matrix metalloproteinases in skin" 6 : 199-213, 1997

      10 Loftus IM, "Matrix metalloproteinases and atherosclerotic plaque instability" 89 : 680-694, 2002

      11 Aimes RT, "Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments" 270 : 5872-5876, 1995

      12 Shah PK, "Matrix metalloproteinase hypothesis of plaque rupture: players keep piling up but questions remain" 104 : 1878-1880, 2001

      13 Sluijter JP, "Matrix metalloproteinase 2 is associated with stable and matrix metalloproteinases 8 and 9 with vulnerable carotid atherosclerotic lesions: a study in human endarterectomy specimen pointing to a role for different extracellular matrix metalloproteinase inducer glycosylation forms" 37 : 235-239, 2006

      14 Kunte H, "Markers of instability in high-risk carotid plaques are reduced by statins" 47 : 513-522, 2008

      15 Virmani R, "Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions" 20 : 1262-1275, 2000

      16 Turu MM, "Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound" 187 : 161-169, 2006

      17 Nikkari ST, "Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis" 92 : 1393-1398, 1995

      18 Loftus IM, "Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption" 31 : 40-47, 2000

      19 Galis ZS, "Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques" 94 : 2493-2503, 1994

      20 Li Z, "Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions" 148 : 121-128, 1996

      21 Nagao T, "Increase in extracranial atherosclerotic carotid lesions in patients with brain ischemia in Japan. An angiographic study" 25 : 766-770, 1994

      22 Shah PK, "Human monocyte-derived macrophages induce collagen nbreakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture" 92 : 1565-1569, 1995

      23 Redgrave JN, "Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study" 113 : 2320-2328, 2006

      24 Spagnoli LG, "Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke" 292 : 1845-1852, 2004

      25 Katsumata T, "Extracranial carotid plaque is increasing in Japanese ischemic stroke patients" 116 : 20-25, 2007

      26 Sukhova GK, "Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques" 99 : 2503-2509, 1999

      27 Rothwell PM, "European Carotid Surgery Trialist’s Collaboration. Reanalysis of the final results of the European Carotid Surgery Trial" 34 : 514-523, 2003

      28 Morgan AR, "Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics" 35 : 1310-1315, 2004

      29 Bassiouny HS, "Critical carotid stenoses: morphologic and chemical similarity between symptomatic and asymptomatic plaques" 9 : 202-212, 1989

      30 Falk E, "Coronary plaque disruption" 92 : 657-671, 1995

      31 Suzue A, "Comparison between early and late carotid endarterectomy for symptomatic carotid stenosis in relation to oxidized low-density lipoprotein and plaque vulnerability" 46 : 870-875, 2007

      32 Fisher M, "Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis" 36 : 253-257, 2005

      33 European Carotid Plaque Study Group, "Carotid artery plaque composition--relationship to clinical presentation and ultrasound B-mode imaging" 10 : 23-30, 1995

      34 Jeziorska M, "Calcification in atherosclerotic plaque of human carotid arteries: associations with mast cells and macrophages" 185 : 10-17, 1998

      35 Barnett HJ, "Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators" 339 : 1415-1425, 1998

      36 Carr S, "Atherosclerotic plaque rupture in symptomatic carotid artery stenosis" 23 : 755-765, 1996

      37 Kolodgie FD, "Apoptosis in atherosclerosis. Does it contribute to plaque instability" 19 : 127-139, 2001

      38 Higashikata T, "Altered expression balance of matrix metalloproteinases and their inhibitors in human carotid plaque disruption: results of quantitative tissue analysis using real-time RT-PCR method" 185 : 165-172, 2006

      39 van Oostrom O, "Age-related changes in plaque composition: a study in patients suffering from carotid artery stenosis" 14 : 126-134, 2005

      40 Lovett JK, "A critical appraisal of the performance, reporting, and interpretation of studies comparing carotid plaque imaging with histology" 36 : 1091-1097, 2005

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