Relationship of matrix metalloproteinases and macrophages to embolization during endoluminal carotid interventions

Purpose: To investigate if relationships exist among macrophage infiltration, plasma matrix metalloproteinase (MMP) levels, and the number of emboli generated during endoluminal carotid interventions. Methods: Carotid endarterectomy specimens excised as intact cylinders (n=27) were subjected to a standardized angioplasty procedure under radiological guidance in an ex vivo pulsatile flow model. Emboli collected in distal filters were counted and sized using microscopy. Preoperative plasma gelatinase activity was determined by gelatin zymography and quantified using image analysis software. Levels of tissue inhibitors of metalloproteinases (TIMP) 1 and 2 were determined by ELISA. Macrophages within postangioplasty plaques were analyzed using immunohistochemical staining for CD68 antigen and graded by a blinded examiner. Statistical analysis was performed using Spearman's rank correlation. Results: The median number of emboli recorded during angioplasty was 104 (interquartile range 33.75-242.5, absolute range 13-1090). Plasma MMP-9 and MMP-2 levels correlated with emboli number (r=0.544 [p=0.003] and r=0.412, [p=0.033], respectively), while TIMP-1 and TIMP-2 levels did not. Macrophage infiltration within the plaques correlated with emboli number (r=0.722, p<0.001) and the plasma MMP-9 level (r=0.489, p=0.010). Conclusions: These data indicate that plaque macrophage infiltration may play a role in the generation of emboli during endoluminal carotid intervention, possibly via modulation of protease activity.