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Original research
Overexpression of matrix metalloproteinase-9 is correlated with carotid intraplaque hemorrhage in a swine model
  1. Xiao-Bing Jiang1,
  2. Jin-Shan Wang1,
  3. Dong-Hong Liu2,
  4. Wei-Si Yuan1,
  5. Zhong-Song Shi1
  1. 1Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  2. 2Department of Ultrasound Imaging, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  3. X-BJ and J-SW contributed equally
  1. Correspondence to Dr Zhong-Song Shi, Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; zhongsongshi{at}


Objective Carotid intraplaque hemorrhage may result in rapid worsening of stenosis and thrombus formation leading to stroke in patients with carotid atherosclerosis. The purpose of this study was to assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with carotid plaque and intraplaque hemorrhage in a swine model.

Methods Carotid atherosclerosis was induced in miniswine using a combination of partial ligation and a high cholesterol diet. The carotid artery and rete mirabile were obtained for histopathological and immunohistochemical studies at 3 months. Atherosclerotic changes were classified by Stary stage according to the American Heart Association and the features of vulnerable carotid plaque were assessed. The association of MMP-9 expression in the carotid plaque with intraplaque hemorrhage was analyzed.

Results One hundred and ninety-one carotid segments from 10 carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 had advanced plaque (Stary stage IV–VI). Atheroemboli were found in all 10 rete mirabili, confirming the presence of vulnerable ipsilateral carotid plaques. There was a trend to increased MMP-9 expression in the group with advanced plaque. Areas positive for MMP-9 were significantly greater in plaques with intraplaque hemorrhage than in those without intraplaque hemorrhage (11.84±1.22% vs 6.63±0.59%, p<0.001).

Conclusions Increased expression of MMP-9 is associated with intraplaque hemorrhage in a swine model of vulnerable carotid atherosclerosis.

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