Open AccessCarotid Atherosclerotic Plaque Matrix Metalloproteinase‐12–Positive Macrophage Subpopulation Predicts Adverse Outcome After Endarterectomy
Author(s) -
Scholtes Vincent P. W.,
Johnson Jason L.,
Jenkins Nicholas,
SalaNewby Graciela B.,
Vries JeanPaul P. M.,
Borst Gert Jan,
Kleijn Dominique P. V.,
Moll Frans L.,
Pasterkamp Gerard,
Newby Andrew C.
Publication year - 2012
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.001040
Subject(s) - medicine , cd68 , carotid endarterectomy , quartile , hazard ratio , matrix metalloproteinase , pathology , endarterectomy , gastroenterology , immunohistochemistry , stroke (engine) , odds ratio , confidence interval , carotid arteries , mechanical engineering , engineering
Background Matrix metalloproteinase‐12 ( MMP ‐12) promotes atherosclerosis in animal models. MMP ‐12 is expressed in only a subset of foam‐cell macrophages ( FCM s) in human plaques. We investigated whether the prevalence of this MMP ‐12–expressing subpopulation is a prognostic indicator of adverse outcome in patients after carotid endarterectomy ( CEA ). Methods and Results Serial sections of culprit lesions from 236 patients who underwent CEA and had undergone 3 years of clinical follow‐up were stained immunocytochemically for MMP ‐12 and for CD 68, and the MMP ‐12/ CD 68 ratio was used to quantify the MMP ‐12–expressing subpopulation. A high MMP ‐12/ CD 68 ratio correlated with a high content of lipid and total macrophages and a low content of vascular smooth muscle cells, as well as with MMP ‐8 ( R =0.211, P =0.001), MMP ‐9 ( R =0.251, P <0.001), and cleaved caspase‐3 ( R =0.142, P =0.036) activity measured in a neighboring segment. Dual immunohistochemical examination confirmed the location of MMP ‐12 in a subpopulation of MMP ‐8– and MMP ‐9–positive FCM s, whereas all apoptotic FCM s were MMP ‐12 positive. Patients who yielded plaques within the highest quartile compared with the lowest quartile of MMP ‐12/ CD 68 ratio had a 2.4‐fold (hazard ratio, 2.4; 95% CI, 1.1‐ to 5.1‐fold; adjusted P =0.027) increased risk of major adverse cardiovascular event and a 3.4‐fold (3.4; 1.2‐ to 9.6‐fold, P =0.024) increased risk for stroke. Conclusions The prevalence of an MMP ‐12–positive subset of FCM s is a prognostic marker for adverse clinical outcome after CEA.