Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction.
OBJECTIVE
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.


BACKGROUND
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.


METHODS
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 microg/kg/day for 7 consecutive days) (MI/Ro) or saline (MI/C).


RESULTS
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)-beta1 in the infarcted site on day 3 after MI was decreased in MI/Ro compared with MI/C. In the infarcted site, TGF-beta1, 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.


CONCLUSIONS
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.
Maekawa
Yuichiro
Y
Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Anzai
Toshihisa
T
Yoshikawa
Tsutomu
T
Sugano
Yasuo
Y
Mahara
Keitaro
K
Kohno
Takashi
T
Takahashi
Toshiyuki
T
Ogawa
Satoshi
S
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003331:Coronary Vessels; D004452:Echocardiography; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006339:Heart Rate; D008026:Ligation; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
D018932:Chemokine CCL2; D024042:Collagen Type I; D024061:Collagen Type III; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C036866:romurtide