Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes.
OBJECTIVE
The current study was designed to examine whether ubiquitin expression is higher in unstable than in stable lesions of patients with acute coronary syndrome (ACS).


BACKGROUND
The ubiquitin system has been identified as the nonlysosomal pathway of protein degradation; it is involved in a number of biologic processes crucial to cell and tissue integrity and therefore, might be potentially involved in the rupture of unstable coronary plaques.


METHODS
We conducted an autopsy-based study of 25 consecutive patients with fatal ACS. Lesions of both infarct-related and noninfarct-related segments from the same patients were examined for the expression and localization of ubiquitin by use of immunohistochemistry and a semiquantitative grading scale.


RESULTS
Ubiquitin immunoreactivity was higher in infarct-related than in noninfarct-related lesions (1.4 +/- 0.5 vs. 1.1 +/- 0.6, p = 0.03). Compared with areas adjacent to the plaque (0.6 +/- 0.7), ubiquitin immunoreactivity was higher in areas around the lipid core (2.5 +/- 0.8, p < 0.001), plaque shoulders (1.6 +/- 1.1, p < 0.001), and fibrous cap regions (1.6 +/- 1.1, p < 0.001). Within the plaque area, co-localization of ubiquitin immunoreactivity with T cells and macrophages was found. In areas adjacent to the plaque, ubiquitin immunoreactivity co-localized with neointima cells and media smooth muscle cells.


CONCLUSIONS
In patients with ACS, ubiquitin immunoreactivity is enhanced in unstable, infarct-related lesions, predominantly in plaque regions of tissue degradation. Based on these findings, this study suggests a role for the ubiquitin system in the destabilization and rupture of coronary atherosclerotic plaques in humans.
Herrmann
Joerg
J
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA
Edwards
William D
WD
Holmes
David R
DR
Shogren
Kris L
KL
Lerman
Lilach O
LO
Ciechanover
Aaron
A
Lerman
Amir
A
D000208:Acute Disease; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D001344:Autopsy; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008910:Minnesota; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D012720:Severity of Illness Index; D013577:Syndrome; D025801:Ubiquitin / Q000276:immunology*
D015415:Biomarkers; D025801:Ubiquitin