Fd. Kolodgie et al., Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death, AM J PATH, 157(4), 2000, pp. 1259-1268
Citations number
37
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Although apoptosis is a well-recognized phenomenon in chronic atherosclerot
ic disease, its role in sudden coronary death, in particular, acute plaque
rupture is unknown, Culprit lesions from 40 cases of sudden coronary death
were evaluated. Cases were divided into two mechanisms of death: ruptured p
laques with acute thrombosis (n = 25) and stable plaques with and without h
ealed myocardial infarction (n = 15). Apoptotic cells were identified by st
aining of fragmented DNA and confirmed in select cases by gold conjugate la
beling combined with ultrastructural analysis. Additional studies were perf
ormed to examine the expression and activation of two inducers of apoptosis
, caspases-1 and -3. Ruptured plaques showed extensive macrophage infiltrat
ion of the fibrous cap, in particular at rupture sites contrary to stable l
esions, which contained fewer inflammatory cells, Among the culprit lesions
, the overall incidence of apoptosis in fibrous caps was significantly grea
ter in, ruptured plaques (P < 0.001) and was predominantly localized to the
CD68-positive macrophages, Furthermore, aa optosis at plaque rupture sites
was more frequent than in areas of intact fibrous cap (P = 0.028), Plaque
rupture sites demonstrated a strong immunoreactivity to caspase-1 within th
e apoptotic macrophages; staining for caspase-3 was weak. Immunoblot analys
is of ruptured plaques demonstrated caspase-1 upregulation and the presence
of its active p20 subunit whereas stable lesions showed only the precursor
; nonatherosclerotic control segments were negative for both precursor and
active enzyme, These findings demonstrate extensive apoptosis of macrophage
s limited to the site of plaque rupture. The proteolytic cleavage of caspas
e-1 In ruptured plaques suggests activation of this apoptotic precursor. wh
ether macrophage apoptosis is essential to acute plaque rupture or is a res
ponse to the rupture itself remains to be determined.