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Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction.
J Am Coll Cardiol. 2004 Oct 06; 44(7):1510-20.JACC

Abstract

OBJECTIVES

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.

Authors+Show Affiliations

Division of Cardiology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15464336

Citation

Maekawa, Yuichiro, et al. "Effect of Granulocyte-macrophage Colony-stimulating Factor Inducer On Left Ventricular Remodeling After Acute Myocardial Infarction." Journal of the American College of Cardiology, vol. 44, no. 7, 2004, pp. 1510-20.
Maekawa Y, Anzai T, Yoshikawa T, et al. Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol. 2004;44(7):1510-20.
Maekawa, Y., Anzai, T., Yoshikawa, T., Sugano, Y., Mahara, K., Kohno, T., Takahashi, T., & Ogawa, S. (2004). Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction. Journal of the American College of Cardiology, 44(7), 1510-20.
Maekawa Y, et al. Effect of Granulocyte-macrophage Colony-stimulating Factor Inducer On Left Ventricular Remodeling After Acute Myocardial Infarction. J Am Coll Cardiol. 2004 Oct 6;44(7):1510-20. PubMed PMID: 15464336.
* Article titles in AMA citation format should be in sentence-case
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, PY - 2004/01/27/received PY - 2004/04/12/revised PY - 2004/05/19/accepted PY - 2004/10/7/pubmed PY - 2004/10/28/medline PY - 2004/10/7/entrez SP - 1510 EP - 20 JF - Journal of the American College of Cardiology JO - J Am Coll Cardiol VL - 44 IS - 7 N2 - OBJECTIVES: 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. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/15464336/Effect_of_granulocyte_macrophage_colony_stimulating_factor_inducer_on_left_ventricular_remodeling_after_acute_myocardial_infarction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(04)01361-0 DB - PRIME DP - Unbound Medicine ER -