DIRECT TRANSFER OF TRANSFORMING GROWTH-FACTOR-BETA-1 GENE INTO ARTERIES STIMULATES FIBROCELLULAR HYPERPLASIA

被引:348
作者
NABEL, EG
SHUM, L
POMPILI, VJ
YANG, ZY
SAN, H
SHU, HB
LIPTAY, S
GOLD, L
GORDON, D
DERYNCK, R
NABEL, GJ
机构
[1] UNIV MICHIGAN,MED CTR,DEPT BIOL CHEM,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,MED CTR,DEPT PATHOL,ANN ARBOR,MI 48109
[3] UNIV MICHIGAN,MED CTR,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109
[4] UNIV CALIF SAN FRANCISCO,DEPT GROWTH & DEV,SAN FRANCISCO,CA 94143
[5] UNIV CALIF SAN FRANCISCO,DEPT ANAT,PROGRAM CELL BIOL,SAN FRANCISCO,CA 94143
[6] UNIV CALIF SAN FRANCISCO,DEPT ANAT,PROGRAM DEV BIOL,SAN FRANCISCO,CA 94143
[7] NYU,DEPT PATHOL,NEW YORK,NY 10016
关键词
GENE TRANSFER; GENE EXPRESSION; EXTRACELLULAR MATRIX; CELLULAR PROLIFERATION;
D O I
10.1073/pnas.90.22.10759
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor beta1 (TGF-beta1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-beta1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-beta1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-beta1 into porcine arteries. Expression of TGF-beta1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-beta1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-beta1 was greater, and cellular proliferation was less prominent. These findings show that TGF-beta1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.
引用
收藏
页码:10759 / 10763
页数:5
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