Relationship of matrix metalloproteinases and macrophages to embolization during endoluminal carotid interventions.
OBJECTIVE
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.
Bicknell
Colin D
CD
Regional Vascular Unit, Department of Surgical Oncology, Imperial College, London, England, UK. colin.bicknell@ic.ac.uk
Peck
David
D
Alkhamesi
Nawar A
NA
Cowling
Mark G
MG
Clark
Martin W
MW
Goldin
Robert
R
Foale
Rodney
R
Jenkins
Michael P
MP
Wolfe
John H
JH
Darzi
Ara W
AW
Cheshire
Nicholas J
NJ
D017130:Angioplasty / Q000009:adverse effects*; D002343:Carotid Artery, Internal / Q000201:enzymology / Q000601:surgery*; D016893:Carotid Stenosis / Q000201:enzymology / Q000601:surgery; D004617:Embolism / Q000201:enzymology* / Q000209:etiology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008955:Models, Cardiovascular; D011673:Pulsatile Flow; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases