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PMID: 7639325 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 beta-converting enzyme.

The American journal of pathology ·Vol. 147 ·No. 2 ·1995-08-00 ·Pages 251-66

Geng YJ, Libby P

Abstract

This study sought evidence for apoptosis, a form of programmed cell death, in human atheromatous coronary and carotid arteries. Markers for apoptotic cells included in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), genomic DNA electrophoresis, and morphological analysis. Intimal lesions contained more TUNEL+ cells (34 +/- 6%, n = 8) than non-atherosclerotic arterial intima (8 +/- 3%, n = 5, P < 0.05). The tunica media of the diseased arteries had a percentage of TUNEL+ cells (5 +/- 1%) similar to that in the normal vessels (3 +/- 1%, N.S.). Oligonucleosomal DNA fragments were visualized in extracts from 12 atheromatous plaques but in none of 5 non-atherosclerotic vessels. Both smooth muscle cells (SMC) and macrophages, two major cell types in the atherosclerotic intima, bore markers of apoptosis, but with different patterns, as determined by double histochemical labeling for cell types and TUNEL. The TUNEL+ SMC localized mainly in the fibrotic portion of the atheroma, whereas TUNEL+ macrophages clustered near or within the lipid-rich core of the lesion. Atheromatous lesions expressed mRNA encoding interleukin-1 beta-converting enzyme (ICE), a mammalian cell death gene, as demonstrated by reverse transcriptase polymerase chain reaction. Immunohistochemistry revealed that ICE localized in regions of TUNEL+ SMC and macrophages. TUNEL- cells showed little or no immunoreactive ICE. These data point to a role for apoptosis in regulation of cell accumulation during atherogenesis and suggest involvement of ICE in SMC death in fibrous regions of complex atheroma, and in macrophage death in the lipid-rich core of the lesion. Apoptosis of vascular cells in fibrous cap may impede maintenance or repair of the matrix in this region and affect stability of the plaques.

MeSH Terms
Apoptosis Arteries Arteriosclerosis/genetics,metabolism,pathology Base Sequence Biomarkers Caspase 1 Coronary Vessels/metabolism,pathology Cysteine Endopeptidases/genetics,metabolism DNA Damage Humans Macrophages/pathology Molecular Sequence Data Muscle, Smooth, Vascular/pathology Oligonucleotide Probes/genetics RNA, Messenger/metabolism Reference Values Tissue Distribution Tunica Intima/metabolism,pathology
Chemicals
Biomarkers Oligonucleotide Probes RNA, Messenger Cysteine Endopeptidases Caspase 1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Geng Y J
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Libby P
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1995-08-00
Pages
251-66
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1869820
Subset
IM
Grants
NHLBI NIH HHS · HL-34636 · United States
Corrections
CommentIn
PMID: 7639321
External Links
PubMed source PMC Full Text View journal details
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