Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome.
Circulation
; 116(11): 1226-33, 2007 Sep 11.
Article
in En
| MEDLINE
| ID: mdl-17709641
ABSTRACT
BACKGROUND:
The endoplasmic reticulum (ER) responds to various stresses by upregulation of ER chaperones, but prolonged ER stress eventually causes apoptosis. Although apoptosis is considered to be essential for the progression and rupture of atherosclerotic plaques, the influence of ER stress and apoptosis on rupture of unstable coronary plaques remains unclear. METHODS ANDRESULTS:
Coronary artery segments were obtained at autopsy from 71 patients, and atherectomy specimens were obtained from 40 patients. Smooth muscle cells and macrophages in the fibrous caps of thin-cap atheroma and ruptured plaques, but not in the fibrous caps of thick-cap atheroma and fibrous plaques, showed a marked increase of ER chaperone expression and apoptotic cells. ER chaperones also showed higher expression in atherectomy specimens from patients with unstable angina pectoris than in specimens from those with stable angina. Expression of 7-ketocholesterol was increased in the fibrous caps of thin-cap atheroma compared with thick-cap atheroma. Treatment of cultured coronary artery smooth muscle cells or THP-1 cells with 7-ketocholesterol induced upregulation of ER chaperones and apoptosis, whereas these changes were prevented by antioxidants. We also investigated possible signaling pathways for ER-initiated apoptosis and found that the CHOP (a transcription factor induced by ER stress)-dependent pathway was activated in unstable plaques. In addition, knockdown of CHOP expression by small interfering RNA decreased ER stress-dependent death of cultured coronary artery smooth muscle cells and THP-1 cells.CONCLUSIONS:
Increased ER stress occurs in unstable plaques. Our findings suggest that ER stress-induced apoptosis of smooth muscle cells and macrophages may contribute to plaque vulnerability.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Coronary Artery Disease
/
Myocardial Ischemia
/
Endoplasmic Reticulum
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Circulation
Year:
2007
Document type:
Article
Affiliation country:
Japan