Expression of endothelin-1, endothelin-3, endothelin-converting enzyme-1, and endothelin-A and endothelin-B receptor mRNA after angioplasty-induced neointimal formation in the rat

被引:130
作者
Wang, XK [1 ]
Douglas, SA [1 ]
Louden, C [1 ]
VickeryClark, LM [1 ]
Feuerstein, GZ [1 ]
Ohlstein, EH [1 ]
机构
[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT EXPTL PATHOL,KING OF PRUSSIA,PA 19406
关键词
endothelin system; neointimal formation; balloon angioplasty; reverse transcription/polymerase chain reaction;
D O I
10.1161/01.RES.78.2.322
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Endothelins (ETs) are potent vasoconstrictors known to play a role in tissue remodeling after vascular wall injury. The molecular mechanisms for the expression and functions of ETs and their receptors after carotid artery angioplasty are not fully understood. Using quantitative reverse transcription and polymerase chain reaction, the present study demonstrates the temporal mRNA expression of ET-converting enzyme-1 (ECE-1), preproET-1, preproET-3, and both ET(a) and ET(B) receptors after rat carotid artery balloon angioplasty. A significant increase in ECE-1 mRNA was observed at 6 hours (1.8-fold increase over control, P<.01) and 24 hours (1.7-fold increase, P<.01) in carotid arteries after angioplasty. In contrast, a significant increase in preproET-1 mRNA levels was not observed until 3 days (1.9-fold increase, P<.05) and 7 days (2.1-fold increase, P<.05). A similarly delayed increase in preproET-3 mRNA was observed at 7 days (2.8-fold increase, P<.05) and 14 days (2.6-fold increase, P<.05) after angioplasty. A parallel but marked increase in ET(A) and ET(B) receptor mRNAs compared with preproET-1 and -3 messages was observed after angioplasty. The levels of ET(A) receptor mRNA were elevated 29.3-fold (P<.001) and 24.3-fold (P<.01) at 3 and 7 days, respectively, after angioplasty. The increase in ET(B) receptor mRNA occurred slightly earlier than the increase in ET(A) receptor mRNA, showing 15.1-fold increase at 1 day (P<.001) and 11.3-fold increase at 3 days (P<.01) after angioplasty. Immunohistochemical studies using anti-ET antibodies demonstrated a corresponding increase in ET immunoactivity, which was distributed mainly in the neointimal cells 14 days after angioplasty. The increases in ECE-1, ET-1, and ET-3 and their receptor expression after balloon angioplasty suggest that these proteins play in active role in the pathogenesis of neointimal formation.
引用
收藏
页码:322 / 328
页数:7
相关论文
共 37 条
[1]   CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR [J].
ARAI, H ;
HORI, S ;
ARAMORI, I ;
OHKUBO, H ;
NAKANISHI, S .
NATURE, 1990, 348 (6303) :730-732
[2]   ROLE OF ENDOTHELIN-1 IN NEOINTIMA FORMATION AFTER ENDOTHELIAL REMOVAL IN RABBIT CAROTID ARTERIES [J].
AZUMA, H ;
HAMASAKI, H ;
NIIMI, Y ;
TERADA, T ;
MATSUBARA, O .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1994, 267 (06) :H2259-H2267
[3]   TRANSCRIPTION OF THE DYSTROPHIN GENE IN HUMAN-MUSCLE AND NON-MUSCLE TISSUES [J].
CHELLY, J ;
KAPLAN, JC ;
MAIRE, P ;
GAUTRON, S ;
KAHN, A .
NATURE, 1988, 333 (6176) :858-860
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]  
DOUGLAS SA, 1995, CARDIOVASC RES, V29, P641, DOI 10.1016/0008-6363(96)88634-2
[6]   ENDOTHELIN-1 PROMOTES NEOINTIMA FORMATION AFTER BALLOON ANGIOPLASTY IN THE RAT [J].
DOUGLAS, SA ;
OHLSTEIN, EH .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1993, 22 :S371-S373
[7]   A ROLE FOR ENDOGENOUS ENDOTHELIN-1 IN NEOINTIMAL FORMATION AFTER RAT CAROTID-ARTERY BALLOON ANGIOPLASTY - PROTECTIVE EFFECTS OF THE NOVEL NONPEPTIDE ENDOTHELIN RECEPTOR ANTAGONIST SB-209670 [J].
DOUGLAS, SA ;
LOUDEN, C ;
VICKERYCLARK, LM ;
STORER, BL ;
HART, T ;
FEUERSTEIN, GZ ;
ELLIOTT, JD ;
OHLSTEIN, EH .
CIRCULATION RESEARCH, 1994, 75 (01) :190-197
[8]   QUANTITATIVE-ANALYSIS OF POLYMERASE CHAIN-REACTION PRODUCTS USING BIOTINYLATED DUTP INCORPORATION [J].
DUPLAA, C ;
COUFFINHAL, T ;
LABAT, L ;
MOREAU, C ;
LAMAZIERE, JMD ;
BONNET, J .
ANALYTICAL BIOCHEMISTRY, 1993, 212 (01) :229-236
[9]   PHENOTYPIC CHANGE OF ENDOTHELIN RECEPTOR SUBTYPE IN CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS [J].
EGUCHI, S ;
HIRATA, Y ;
IMAI, T ;
KANNO, K ;
MARUMO, F .
ENDOCRINOLOGY, 1994, 134 (01) :222-228
[10]   ANALYSIS OF CYTOKINE MESSENGER-RNA AND DNA - DETECTION AND QUANTITATION BY COMPETITIVE POLYMERASE CHAIN-REACTION [J].
GILLILAND, G ;
PERRIN, S ;
BLANCHARD, K ;
BUNN, HF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (07) :2725-2729