Effect of AT(1) receptor blockade on cardiac collagen remodeling after myocardial infarction

被引:89
作者
Ju, HS [1 ]
Zhao, SF [1 ]
Jassal, DS [1 ]
Dixon, IMC [1 ]
机构
[1] UNIV MANITOBA,ST BONIFACE GEN HOSP,RES CTR,FAC MED,MOL CARDIOL LAB,INST CARDIOVASC SCI,WINNIPEG,MB R2H 2A6,CANADA
基金
英国医学研究理事会;
关键词
collagen remodeling; gene expression; myocardial infarction; prolyl; 4-hydroxylase; immunohistochemistry; losartan; rat; ventricle;
D O I
10.1016/S0008-6363(97)00130-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Previous work has shown that cardiac fibrosis occurs after myocardial infarction (MI) in non-infarcted ventricular tissue and that this event is associated with abnormal cardiac function. Our aim was to investigate the effect of AT, receptor blockade on cardiac collagen remodeling in post-MI rat heart remote from the infarct site by addressing collagen mRNA abundance, posttranslational hydroxylation of collagen monomers, and mature collagen deposition. Prolyl 4-hydroxylase (PH) mediates hydroxylation of procollagen a-chains in the endoplasmic reticulum of cardiac fibroblasts and thus regulates the downstream formation and secretion of helical procollagen molecules, Methods: The effects of losartan (15 mg/kg/day) on collagen deposition and mRNA abundance were monitored in viable left and right ventricles in sham-operated (control) and experimental groups in the presence or absence of losartan. Immunoreactive PH concentration in viable tissues as well as cardiac function in control and experimental groups was determined by ELISA. Results: Immunohistochemical staining and 4-hydroxyproline assays confirmed that losartan treatment attenuates fibrosis in experimental hearts. Northern analysis revealed that losartan treatment of 1, 2, or 4 week experimental groups had no effect on collagen mRNA abundance compared to untreated post-MI rats. On the other hand, immunoreactive PH concentration was significantly decreased in the post-MI group treated with losartan, Determination of cardiac mass and cardiac function revealed that losartan treatment was associated with attenuated cardiac hypertrophy and improved left ventricular (LV) function in experimental animals. Conclusions: AT(1) blockade is associated with a significant decrease in cardiac fibrosis in treated post-MI rats, and this trend is positively correlated to a significant decrease in immunoreactive PH compared to untreated experimental animals. The expression of cardiac PH may be regulated by angiotensin via AT(1) receptor activation, and the suppression of PH with losartan treatment may be an important mechanism for modulation of collagen deposition in the post-MI rat heart. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:223 / 232
页数:10
相关论文
共 47 条
[1]  
ALBERTS B, 1994, MOL BIOL CELL, P972
[2]   IMMUNOLOGICAL PROPERTIES OF MONOCLONAL-ANTIBODIES TO HUMAN AND RAT PROLYL 4-HYDROXYLASE [J].
BAI, Y ;
MURAGAKI, Y ;
OBATA, K ;
IWATA, K ;
OOSHIMA, A .
JOURNAL OF BIOCHEMISTRY, 1986, 99 (06) :1563-1570
[3]   NONSYNCHRONOUS CHANGES IN MYOCARDIAL COLLAGEN MESSENGER-RNA AND PROTEIN DURING AGING - EFFECT OF DOCA-SALT HYPERTENSION [J].
BESSE, S ;
ROBERT, V ;
ASSAYAG, P ;
DELCAYRE, C ;
SWYNGHEDAUW, B .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1994, 267 (06) :H2237-H2244
[4]   MOLECULAR SIGNALING MECHANISMS CONTROLLING GROWTH AND FUNCTION OF CARDIAC FIBROBLASTS [J].
BOOZ, GW ;
BAKER, KM .
CARDIOVASCULAR RESEARCH, 1995, 30 (04) :537-543
[5]   EFFICACY OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION AND AT(1) RECEPTOR BLOCKADE ON CARDIAC PUMP PERFORMANCE AFTER MYOCARDIAL-INFARCTION IN RATS [J].
CAPASSO, JM ;
LI, P ;
MEGGS, LG ;
HERMAN, MV ;
ANVERSA, P .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 23 (04) :584-593
[6]  
CHAN YL, 1984, J BIOL CHEM, V259, P224
[7]   A BIOCHEMICAL METHOD FOR THE QUANTITATION OF MYOCARDIAL SCARRING AFTER EXPERIMENTAL CORONARY-ARTERY OCCLUSION [J].
CHIARIELLO, M ;
AMBROSIO, G ;
CAPPELLIBIGAZZI, M ;
PERRONEFILARDI, P ;
BRIGANTE, F ;
SIFOLA, C .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1986, 18 (03) :283-290
[8]   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
[9]   CLONING AND CHARACTERIZATION OF 5 OVERLAPPING CDNAS SPECIFIC FOR THE HUMAN PRO-ALPHA-1(I) COLLAGEN CHAIN [J].
CHU, ML ;
MYERS, JC ;
BERNARD, MP ;
DING, JF ;
RAMIREZ, F .
NUCLEIC ACIDS RESEARCH, 1982, 10 (19) :5925-5934
[10]  
CHU ML, 1985, J BIOL CHEM, V260, P4357