title: Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome.
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.
  
  
  RESULTS
  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.
authors: Department of Cardiovascular Medicine, National Cardiovascular Center, Suita, Osaka 565-8565, Japan.
authors: Masafumi
authors: M
authors: Myoishi
authors: Hiroyuki
authors: H
authors: Hao
authors: Tetsuo
authors: T
authors: Minamino
authors: Kouki
authors: K
authors: Watanabe
authors: Kensaku
authors: K
authors: Nishihira
authors: Kinta
authors: K
authors: Hatakeyama
authors: Yujiro
authors: Y
authors: Asada
authors: Ken-ichiro
authors: K
authors: Okada
authors: Hatsue
authors: H
authors: Ishibashi-Ueda
authors: Giulio
authors: G
authors: Gabbiani
authors: Marie-Luce
authors: ML
authors: Bochaton-Piallat
authors: Naoki
authors: N
authors: Mochizuki
authors: Masafumi
authors: M
authors: Kitakaze
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018832:Molecular Chaperones