Granulocyte colony-stimulating factor ameliorates coronary artery elastin breakdown in a mouse model of Kawasaki disease.

Abstract

BACKGROUND:

Coronary artery damage from Kawasaki disease (KD) is closely linked to the dysfunction of the endothelial progenitor cells (EPCs). The aim of the present study was to evaluate the modulatory effect of granulocyte colony-stimulating factor (G-CSF) on EPCs and elastin breakdown of coronary arteries in a KD mouse model.

METHODS:

A Lactobacillus casei cell wall extract (LCWE)-induced KD model was established in C57BL/6 mice that were subsequently administrated with recombinant human G-CSF (rhG-CSF). Nω-nitro-L-arginine methyl ester (L-NAME) was administrated for the negative intervention. Evaluations included coronary artery lesions, EPC number and functions, and the plasma concentration of nitric oxide (NO).

RESULTS:

Elastin breakdown was found in the coronary arteries of model mice 56 days after injection of LCWE. The number of circulating EPCs, plasma concentration of NO, and functions of bone marrow EPCs, including proliferation, adhesion, and migration abilities, were all lower in the KD model group compared with those in the control group. After administration of rhG-CSF, the number of circulating EPCs and plasma concentration of NO were increased significantly compared with those in the KD model group. There were also increases in the functional indexes of EPCs. Furthermore, rhG-CSF administration improved the elastin breakdown effectively. However, these protective effects of rhG-CSF on coronary arteries were attenuated by L-NAME.

CONCLUSION:

The present study indicated that the administration of G-CSF prevents elastin breakdown of the coronary arteries by enhancing the number and functions of EPCs via the NO system, and then accelerates the repair of coronary artery lesions in the KD.

• Authors: Junfeng Liu, Zhi Chen, Zhongdong Du, Dunxiang Lu
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 127 Issue 21 Pg. 3712-7 ( 2014) ISSN: 2542-5641 [Electronic] China
• PMID: 25382324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrogen Oxides
• Granulocyte Colony-Stimulating Factor
• Elastin
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Coronary Vessels (cytology, drug effects, metabolism)
• Disease Models, Animal
• Elastin (metabolism)
• Endothelial Progenitor Cells (cytology)
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Mucocutaneous Lymph Node Syndrome (blood, drug therapy, metabolism)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitrogen Oxides (blood)