Doppler echocardiographic assessment and cardiac gene expression analysis of the left ventricle in myocardial infarcted rats.
The purpose of this study was to examine cardiac geometry and function by Doppler echocardiography and to analyze mRNA expression of cardiac phenotype and extracellular matrix in myocardial infarcted rats. Doppler echocardiograms and hemodynamics were measured 2 weeks after myocardial infarction (MI). mRNA levels in the non-infarcted left ventricle (LV) and infarct site were measured by Northern blot analysis. LV internal diastolic dimension was greater in infarcted (MI) than in sham-operated rats (control) (MI 7.2+/-0.3 mm vs control 4.6+0.3 mm, p<0.01). The fractional shortening decreased in MI rats (MI 32+4% vs control 61+/-3%, p<0.01). Peak early filling velocity increased in MI rats (MI 91+/-5 cm/sec vs control 72+/-4 cm/sec, p<0.05), and deceleration rate of the early filling wave was more rapid in rats with MI (MI 25.1+/-2.8 m/sec2 vs control 12.4+/-1.7 m/sec2, p < 0.01). Late filling velocity decreased (MI 16+/-3 cm/sec vs control 35+/-6 cm/sec, p <0.05), resulting in a marked increase in the ratio of early filling to late filling (MI 7.1+/-1.2 vs control 2.5+/-0.4, p<0.01). mRNA levels for beta-myosin heavy chain (beta-MHC), a-skeletal actin, atrial natriuretic polypeptide (ANP), collagen types I and III, and matrix metalloproteinase 2 (MMP-2) in the non-infarcted LV increased significantly by 1.8-, 2.4-, 4.7-, 2.6-, 2.1- (all p<0.01) and 1.4-fold (p<0.05), respectively, compared with sham-operated myocardium. In the infarct site, mRNA levels for transforming growth factor (TGF)-beta1, collagen types I and III, and MMP-2 significantly increased by 3.2-, 11.0-, 9.7-, and 6.3-fold (all p<0.01), respectively, compared with sham-operated myocardium. Myocardial infarcted rat was characterized by cavity dilation and marked abnormalities of systolic and diastolic function, accompanied by a shift of myocytes to fetal phenotype and activation of collagen genes in the non-infarcted myocardium.
Shimizu
N
N
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Yoshiyama
M
M
Takeuchi
K
K
Hanatani
A
A
Kim
S
S
Omura
T
T
Iwao
H
H
Yoshikawa
J
J
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003971:Diastole; D004452:Echocardiography; D015150:Echocardiography, Doppler; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics; D018093:Gelatinases / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D006352:Heart Ventricles; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000473:pathology
D000199:Actins; D005326:Fetal Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009320:Atrial Natriuretic Factor; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D018995:Myosin Heavy Chains