Effects of different doses of granulocyte colony-stimulating factor mobilization therapy on ischemic cardiomyopathy.

Abstract

G-CSF mobilization might be beneficial to ICM, but the relationship between effect/safety and the dosage of G-CSF remains unclear. In this study, 24 pigs were used to build ICM models and were randomized into four groups. Four weeks later, different dosages of G-CSF were given daily by subcutaneous injection for 5 days. Another 4 weeks later, all the animals were sacrificed. Electrocardiography, coronary arteriography, left ventriculography, transthoracic echocardiography, cardiac MRI, and SPECT, histopathologic analysis, and immunohistochemistry techniques were used to evaluate left ventricular function and myocardial infarct size. Four weeks after G-CSF treatment, pigs in middle-dose G-CSF group exhibited obvious improvements of left ventricular remodeling and function. Moderate G-CSF mobilization ameliorated the regional contractility of ICM, preserved myocardial viability, and reduced myocardial infarct size. More neovascularization and fewer apoptotic myocardial cells were observed in the ischemic region of the heart in middle-dose group. Expression of vWF, VEGF and MCP-1 were up-regulated, and Akt1 was activated in high- and middle-dose groups. Moreover, CRP, TNF-α and S-100 were elevated after high-dose G-CSF mobilization. Middle-dose G-CSF mobilization therapy is an effective and safe treatment for ICM, and probably acts via a mechanism involving promoting neovascularization, inhibiting cardiac fibrosis and anti-apoptosis.

• Authors: Rongchong Huang, Haichen Lv, Kang Yao, Lei Ge, Zhishuai Ye, Huaiyu Ding, Yiqi Zhang, Hao Lu, Zheyong Huang, Shuning Zhang, Yunzeng Zou, Junbo Ge
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 5922 (04 12 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29651017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Cardiomyopathies (drug therapy, pathology)
• Coronary Angiography
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Electrocardiography
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Heart (drug effects, physiopathology)
• Humans
• Myocardial Ischemia (drug therapy, pathology)
• Swine
• Ventricular Function, Left (drug effects, physiology)
• Ventricular Remodeling (physiology)