Determination of temporal expression patterns for multiple genes in the rat carotid artery injury model

被引:23
作者
Tai, JTN
Brooks, EE
Liang, SD
Somogyi, R
Rosete, JD
Lawn, RR
Shiffman, D
机构
[1] CV Therapeut, Palo Alto, CA 94304 USA
[2] Incyte Pharmaceut, Palo Alto, CA USA
关键词
restenosis; carotid artery injury; gene expression profiling; extracellular matrix; matrix metalloproteinases;
D O I
10.1161/01.ATV.20.10.2184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Vascular injury induces extensive alteration to the extracellular matrix (ECM). These changes contribute to lesion formation and promote cell migration and proliferation. To elucidate ECM response to arterial injury, we used real-time polymerase chain reaction monitoring to quantitate the expression levels of 81 genes involved in the synthesis and breakdown of ECM as well as receptors and signaling proteins that communicate and respond to ECM molecules. The temporal regulation of gene expression in the carotid was measured at 1, 3, 5, 7, 9, 14, and 28 days postinjury. Among the 68 genes that showed detectable expression by our method, 47 (69%) were significantly induced or repressed over time, confirming the extensive ECM gene response in this model. More ECM-related genes (31) were regulated at day I than at any other time point, and the number of regulated genes decreased over time. However, lit of the genes were still induced or repressed at day 28, indicating that return to preinjury expression patterns did not occur and no new steady state was achieved over 28 days. In spite of the large number of changes in gene expression, only a small number of expression patterns was observed, suggesting that ECM-related genes could potentially be coregulated.
引用
收藏
页码:2184 / 2191
页数:8
相关论文
共 36 条
[1]   A systematic analysis of 40 random genes in cultured vascular smooth muscle subtypes reveals a heterogeneity of gene expression and identifies the tight junction gene zonula occludens 2 as a marker of epithelioid "pup" smooth muscle cells and a participant in carotid neointimal formation [J].
Adams, LD ;
Lemire, JM ;
Schwartz, SM .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (11) :2600-2608
[2]   The extracellular matrix in balloon arterial injury: A novel target for restenosis prevention [J].
Batchelor, WB ;
Robinson, R ;
Strauss, BH .
PROGRESS IN CARDIOVASCULAR DISEASES, 1998, 41 (01) :35-49
[3]   CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation [J].
Brooks, EE ;
Gray, NS ;
Joly, A ;
Kerwar, SS ;
Lum, R ;
Mackman, RL ;
Norman, TC ;
Rosete, J ;
Rowe, M ;
Schow, SR ;
Schultz, PG ;
Wang, XB ;
Wick, MM ;
Shiffman, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (46) :29207-29211
[4]  
Casterella P J, 1999, Cardiol Rev, V7, P219, DOI 10.1097/00045415-199907000-00014
[5]   Regulation of extracellular matrix gene expression by mechanical stress [J].
Chiquet, M .
MATRIX BIOLOGY, 1999, 18 (05) :417-426
[6]   Regulation of extracellular matrix synthesis by mechanical stress [J].
Chiquet, M ;
Matthisson, M ;
Koch, M ;
Tannheimer, M ;
ChiquetEhrismann, R .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1996, 74 (06) :737-744
[7]  
CLOWES AW, 1983, LAB INVEST, V49, P327
[8]   P1B15 - A CDNA CLONE OF THE RAT MESSENGER-RNA ENCODING CYCLOPHILIN [J].
DANIELSON, PE ;
FORSSPETTER, S ;
BROW, MA ;
CALAVETTA, L ;
DOUGLASS, J ;
MILNER, RJ ;
SUTCLIFFE, JG .
DNA-A JOURNAL OF MOLECULAR & CELLULAR BIOLOGY, 1988, 7 (04) :261-267
[9]  
DHAESELEER P, IN PRESS BIONFORMATI
[10]   Phylogenomics: Improving functional predictions for uncharacterized genes by evolutionary analysis [J].
Eisen, JA .
GENOME RESEARCH, 1998, 8 (03) :163-167