title: Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis. Tissue characteristics compared to primary atherosclerosis.
abstract: 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.
authors.affiliation: Department of Cardiology, University of Bonn, Sigmund-Freud-Strasse 25, DE-53105 Bonn, Germany. Dirk.Skowasch@ukb.uni-bonn.de
authors.forename: Dirk
authors.initials: D
authors.lastname: Skowasch
authors.forename: Alexander
authors.initials: A
authors.lastname: Jabs
authors.forename: René
authors.initials: R
authors.lastname: Andrié
authors.forename: Sabine
authors.initials: S
authors.lastname: Dinkelbach
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schiele
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
authors.forename: Berndt
authors.initials: B
authors.lastname: Lüderitz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bauriedel
mesh_terms: D000368:Aged; D017209:Apoptosis; D001161:Arteriosclerosis / Q000473:pathology; D017225:Atherectomy, Coronary; D015415:Biomarkers; D002455:Cell Division; D002690:Chlamydia Infections / Q000150:complications*; D023903:Coronary Restenosis / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D015607:Stents; D017539:Tunica Intima / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D015415:Biomarkers