APOPTOSIS IN HUMAN ATHEROSCLEROSIS AND RESTENOSIS

被引:629
作者
ISNER, JM [1 ]
KEARNEY, M [1 ]
BORTMAN, S [1 ]
PASSERI, J [1 ]
机构
[1] TUFTS UNIV, SCH MED, ST ELIZABETHS MED CTR, DEPT BIOMED RES, BOSTON, MA 02135 USA
关键词
APOPTOSIS; PROGRAMMED CELL DEATH; PROLIFERATION; BCL-2;
D O I
10.1161/01.CIR.91.11.2703
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Apoptosis has been recognized in normal, including rapidly proliferating, cell populations and is inferred to be potentially responsible for the maintenance of stable cell numbers in tissues with various degrees of proliferative activity. Previous studies performed in rats indicated that despite the persistence of a relatively high level of injury-induced proliferative activity, total arterial smooth muscle content at 12 weeks remained unchanged from that measured at 2 weeks, suggesting that accrual of vascular smooth muscle cells is mitigated by cell death. The extent to which apoptosis may be observed in human atherosclerosis and/or restenosis, however, has not been previously established. Methods and Results We performed immunohistochemical studies on 56 specimens retrieved from patients undergoing directional atherectomy for primary atherosclerotic lesions or recurrent arterial narrowing after percutaneous revascularization (restenosis). Immunohistochemical staining disclosed evidence of apoptosis in 35 (63%) of the 56 specimens studied. When present, immunohistochemical evidence of apoptosis was typically limited to <2% of cells in the specimen. The finding of apoptosis, however, was not distributed equally among four groups of specimens studied. Specimens retrieved from patients with restenosis were more frequently observed to contain foci of apoptosis than specimens retrieved from patients with primary atherosclerotic lesions. Among 14 peripheral arterial specimens from patients with restenosis, 13 (93%) contained foci of apoptosis; in contrast, apoptosis was observed in only 6 (43%) of 14 peripheral specimens from patients with primary lesions (P=.0046). Among coronary arterial specimens, apoptosis was observed in 12 (86%) of 14 specimens from patients with restenosis versus 6 (29%) of 14 specimens from patients with primary obstructions (P<.0075). Conclusions Apoptosis is a feature of human vascular pathology, including restenotic lesions and, to a lesser extent, primary atherosclerotic lesions. The findings of the present study suggest that apoptosis may modulate the cellularity of lesions that produce human vascular obstruction, particularly those-with evidence of more extensive proliferative activity.
引用
收藏
页码:2703 / 2711
页数:9
相关论文
共 58 条
[1]  
ARENDS MJ, 1994, AM J PATHOL, V144, P1045
[2]   INTIMAL PROLIFERATION OF SMOOTH-MUSCLE CELLS AS AN EXPLANATION FOR RECURRENT CORONARY-ARTERY STENOSIS AFTER PERCUTANEOUS TRANS-LUMINAL CORONARY ANGIOPLASTY [J].
AUSTIN, GE ;
RATLIFF, NB ;
HOLLMAN, J ;
TABEI, S ;
PHILLIPS, DF .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1985, 6 (02) :369-375
[3]   A RAPID AND SENSITIVE ASSAY FOR THE DETECTION OF DNA FRAGMENTATION DURING EARLY PHASES OF APOPTOSIS [J].
BASNAKIAN, AG ;
JAMES, SJ .
NUCLEIC ACIDS RESEARCH, 1994, 22 (13) :2714-2715
[4]   DEREGULATED EXPRESSION OF THE C-MYC ONCOGENE ABOLISHES INHIBITION OF PROLIFERATION OF RAT VASCULAR SMOOTH-MUSCLE CELLS BY SERUM REDUCTION, INTERFERON-GAMMA, HEPARIN, AND CYCLIC-NUCLEOTIDE ANALOGS AND INDUCES APOPTOSIS [J].
BENNETT, MR ;
EVAN, GI ;
NEWBY, AC .
CIRCULATION RESEARCH, 1994, 74 (03) :525-536
[5]  
BRUNEVAL P, 1986, ARCH PATHOL LAB MED, V110, P1186
[6]  
CLOWES AW, 1983, LAB INVEST, V49, P327
[7]  
CLOWES AW, 1985, LAB INVEST, V52, P611
[8]   KEY MORPHOLOGICAL FEATURES OF APOPTOSIS MAY OCCUR IN THE ABSENCE OF INTERNUCLEOSOMAL DNA FRAGMENTATION [J].
COHEN, GM ;
SUN, XM ;
SNOWDEN, RT ;
DINSDALE, D ;
SKILLETER, DN .
BIOCHEMICAL JOURNAL, 1992, 286 :331-334
[9]  
ESSED CE, 1983, BRIT HEART J, V49, P393
[10]   THE PROTEIN-KINASE INHIBITOR STAUROSPORINE INDUCES MORPHOLOGICAL-CHANGES TYPICAL OF APOPTOSIS IN MOLT-4 CELLS WITHOUT CONCOMITANT DNA FRAGMENTATION [J].
FALCIERI, E ;
MARTELLI, AM ;
BAREGGI, R ;
CATALDI, A ;
COCCO, L .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 193 (01) :19-25