TY - JOUR
T1 - Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction
AU - Maekawa, Yuichiro
AU - Anzai, Toshihisa
AU - Yoshikawa, Tsutomu
AU - Sugano, Yasuo
AU - Mahara, Keitaro
AU - Kohno, Takashi
AU - Takahashi, Toshiyuki
AU - Ogawa, Satoshi
N1 - Funding Information:
Supported in part by grants for scientific research 14770333 (Dr. Maekawa) and 14570693 (Dr. Anzai) from the Ministry of Education, Science, and Culture of Japan.
PY - 2004/10/6
Y1 - 2004/10/6
N2 - We sought to determine the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) induction on post-myocardial infarction (MI) remodeling, especially in relation to the inflammatory response and myocardial fibrosis. Granulocyte-macrophage colony-stimulating factor modifies wound healing by promoting monocytopoiesis and infiltration of monocytes and macrophages into injured tissue; however, the effect of GM-CSF induction on the infarct healing process and myocardial fibrosis is unclear. A model of MI was produced in Wistar rats by ligation of the left coronary artery. The MI animals were randomized to receive GM-CSF inducer (romurtide 200 μg/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C). Echocardiographic and hemodynamic studies on day 14 revealed increased left ventricular (LV) end-diastolic dimension, decreased fractional shortening, elevated LV end-diastolic pressure, and decreased LV maximum rate of isovolumic pressure development in MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming growth factor (TGF)-β1 in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-β1, collagen type I and type III messenger ribonucleic acid (mRNA) expression on day 3, and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive)were greater in the infarcted site on day 7 than those in MI/C. The GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI.
AB - We sought to determine the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) induction on post-myocardial infarction (MI) remodeling, especially in relation to the inflammatory response and myocardial fibrosis. Granulocyte-macrophage colony-stimulating factor modifies wound healing by promoting monocytopoiesis and infiltration of monocytes and macrophages into injured tissue; however, the effect of GM-CSF induction on the infarct healing process and myocardial fibrosis is unclear. A model of MI was produced in Wistar rats by ligation of the left coronary artery. The MI animals were randomized to receive GM-CSF inducer (romurtide 200 μg/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C). Echocardiographic and hemodynamic studies on day 14 revealed increased left ventricular (LV) end-diastolic dimension, decreased fractional shortening, elevated LV end-diastolic pressure, and decreased LV maximum rate of isovolumic pressure development in MI/Ro compared with MI/C. Immunoblotting showed that expression of transforming growth factor (TGF)-β1 in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-β1, collagen type I and type III messenger ribonucleic acid (mRNA) expression on day 3, and collagen content on day 7 were reduced in MI/Ro compared with MI/C, in association with marked infarct expansion. In MI/Ro, monocyte chemoattractant protein-1 mRNA level and the degree of infiltration of monocyte-derived macrophages (ED-1-positive)were greater in the infarcted site on day 7 than those in MI/C. The GM-CSF induction by romurtide facilitated infarct expansion in association with the promotion of monocyte recruitment and inappropriate collagen synthesis in the infarcted region during the early phase of MI.
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U2 - 10.1016/j.jacc.2004.05.083
DO - 10.1016/j.jacc.2004.05.083
M3 - Article
C2 - 15464336
AN - SCOPUS:4644296825
SN - 0735-1097
VL - 44
SP - 1510
EP - 1520
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -