CLINICAL STUDY
Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes
Joerg Herrmann, MD*,
William D. Edwards, MD ,
David R. Holmes, Jr, MD*,
Kris L. Shogren*,
Lilach O. Lerman, MD, PhD ,
Aaron Ciechanover, MD, PhD and
Amir Lerman, MD*,*
* Division of Cardiovascular Diseases, Rochester, Minnesota, USA
Division of Anatomic Pathology, Rochester, Minnesota, USA
Division of Hypertension Mayo Clinic Rochester, Rochester, Minnesota, USA
Unit of Biochemistry, Faculty of Medicine and the Rapport Institute for Research in Medical Sciences, Technion-Israel Institute of Technology, Haifa, Israel
Manuscript received May 10, 2002;
revised manuscript received July 16, 2002,
accepted July 24, 2002.
* Reprint requests and correspondence: Dr. Amir Lerman, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street SW, Rochester, Minnesota USA55905.
lerman.amir{at}mayo.edu
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | ACS | | acute coronary syndrome | | LDL | | low density lipoprotein | | MI | | myocardial infarction | | RT | | room temperature | | TdT | | terminal deoxynucleotidyl transferase | | TUNEL | | terminal deoxynucleotidyl transferase end labeling |
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