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Increased Expression in human Carotid Plaque and Elevated Serum Level of Heat Shock Protein 27 in patients with Coronary Artery Disease
성균관 대학교 의과대학 내과학교실 삼성서울병원 심장혈관센터¹, 건강의학센터², 통계지원실³, 진단병리과⁴, 혈관외과5
박행기¹, 배성원¹, 강민경¹, 최윤호², 김선우³, 고영혜⁴, 김동익5, 이병붕5, 박정의¹
Objectives : We tried to find the proteins which are involved in the plaque instability of human atherosclerotic plaques. We found increased expression of heat shock protein 27(HSP27) in human carotid atherosclerotic plaques. Since HSP27 has been known as an antiapoptotic factor of the vascular smooth muscle cells(VSMC), we tried to prove the roles of HSP27 in the pathogenesis of atherosclerosis. Methods : We performed 2-dimensional electrophoretic analysis of proteins in the tissue samples from human carotid endarterectomy specimens. The tissue samples(n=10) from plaque area was compared with the normal control samples(n=4) of human renal artery. Using the human VSMC, expression of HSP27 was examined after stimulation of cells with oxidized LDL(ox-LDL), H2O2 and simvastatin. Serum level(ng/mL) of HSP27 was measured by ELISA in patients with acute myocardial infarction(AMI, n=10), unstable angina(UA, n=10), stable angina(SA, n=13), and control subjects(control, n=20). Results : Immunohistochemistry of human carotid atherosclerotic plaques revealed over expressed HSP27 in the plaque area. In cultured human VSMC, HSP27 was increased by the incubation with ox-LDL or H2O2. Simvastatin treatment also increased the cellular level of HSP27. The serum levels of HSP27 was significantly increased in the patients with coronary artery disease(AMI=87.26±43.76, UA=88.00±27.67, SA=61.97±24.08, P<0.05) compared with normal control subjects(44.82±29.92). While the HSP27 level was inversely related with α-tocopherol levels in the serums, it was not correlated well with C-reactive protein(CRP) level. Conclusions : We demonstrated the increased expression of HSP27 in the human atherosclerotic plaques and increased serum levels in the patients with coronary artery disease(CAD). Increased expression of HSP27 in human VSMCs by ox-LDL treatment and reciprocal relationship between the serum levels of HSP27 and α-tocopherol suggest HSP27 as a possible marker of CAD, representing local and/or systemic status of oxidative stress in CAD patients.


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