Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still
incompletely understood. Among others, inflammation, immune
reactions, deregulated cell death and growth have been suggested.
Therefore, atherectomy probes from 21 patients with symptomatic ISR
were analyzed by immunohistochemistry for pathogen burden and
compared to primary target lesions from 20 stable angina patients.
While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and
Helicobacter pylori were not found in ISR, acute and/or persistent
chlamydial infection were present in 6/21 of these lesions (29%).
Expression of human heat shock protein 60 was found in 8/21 of
probes (38%). Indicated by distinct signals of CD68, CD40 and CRP,
inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%)
of ISR cases. Cell density of ISR was significantly higher than
that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2);
p < 0.001). There was no replicating cell as shown by Ki67 or
PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR
specimens (29%). Quantitative analysis revealed lower expression
levels for each intimal determinant in ISR compared to primary
atheroma (all p < 0.05). In summary, human ISR at the time of
clinical presentation is characterized by low frequency of pathogen
burden and inflammation, but pronounced hypercellularity, low
apoptosis and absence of proliferation. Copyright (C) 2004 S.
Karger AG, Basel.