Augmented expression of cardiotrophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat.
Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. To clarify the role of CT-1 and the gp130-signaling pathway during ventricular remodeling after myocardial infarction, we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. At 1, 3, 7, 14, 28 and 56 days (n=12 for each group) after ligation of a coronary artery, tissue samples were obtained from infarct tissue, the ventricular septum and the right ventricle. All animals developed large myocardial infarctions, with infarct sizes ranging from 39.8% to 50.3%. Progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA levels were determined by semiquantitative reverse transcription-polymerase chain reaction using 1 or 5 microg of total RNA followed by Southern blotting. The densitometric analysis of the Southern blots revealed a significant increase in CT-1 and gp130 mRNA levels (P<0.01) compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, the ventricular septum (non-infarcted area) and right ventricle. The protein levels of CT-1 and gp130, determined by Western blot analysis, were significantly increased (P<0.05) compared with those of sham-operated rats, peaked during the acute stage and declined thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells and that the intensity of staining was increased at 7 days post-infarct compared with that in sham-operated rats. An augmented CT-1 and gp130 system thus appears to play an important role during ventricular remodeling after myocardial infarction.
Aoyama
T
T
Department of Cardiovascular Medicine, Kyoto University, Japan. taoyama@kuhp.kyoto-u.ac.jp
Takimoto
Y
Y
Pennica
D
D
Inoue
R
R
Shinoda
E
E
Hattori
R
R
Yui
Y
Y
Sasayama
S
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015139:Blotting, Southern; D015153:Blotting, Western; D003331:Coronary Vessels / Q000378:metabolism; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D004452:Echocardiography; D005347:Fibroblasts / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D015703:Antigens, CD; D016207:Cytokines; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1