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.
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.
Authors: Monte S Willis; W H Davin Townley-Tilson; Eunice Y Kang; Jonathon W Homeister; Cam Patterson Journal: Circ Res Date: 2010-02-19 Impact factor: 17.367
Authors: Adi R Bachar; Lea Scheffer; Andreas S Schroeder; Hiromi K Nakamura; Laura J Cobb; Yun K Oh; Lilach O Lerman; Richard E Pagano; Pinchas Cohen; Amir Lerman Journal: Cardiovasc Res Date: 2010-06-18 Impact factor: 10.787