Objective: Metallothioneins (MTs) are antioxidant proteins expressed in
response to injury. We evaluated MT immunoreactivity in carotid plaques
obtained from asymptomatic and symptomatic patients. We also assessed
the relationship between ultrasonic plaque echodensity, histological
grading, computed tomography findings and MT expression.
Methods and results: In this ongoing prospective study, patients (n =
123, mean age (+/- SD) 68.4 +/- 7.7 years, 97 men) with high-grade
carotid stenosis underwent carotid endarterectomy. Specimens were
assessed histologically and immunohistochemically. Echolucent plaques
(types 1+2) were more common in symptomatic patients (p < 0.0001) and
had more advanced histological lesions (p < 0.0001). Echolucent plaques
expressed MTs (in macrophages, fibroblasts and T-lymphocytes)
significantly more than echogenic plaques (types 3+4) (all p < 0.0001).
MT expression was mainly related to carotid plaque echolucency rather
than the presence of symptoms. MT expression was significantly more
common in advanced histological lesions. Plaques from asymptomatic or
symptomatic patients with abnormal computed tomography findings also
showed increased MT expression. There was a time-dependent fall in MT
expression after cerebrovascular events (p <= 0.011).
Conclusions: MT overexpression may be triggered in unstable plaques as a
local protective factor. There is a need to identify both causative and
protective predictors of the ‘vulnerable plaque’ in the ‘vulnerable
patient’. Further studies are needed to resolve these issues
