title: Effects of G-CSF on serum cholesterol and development of atherosclerotic plaque in apolipoprotein E-deficient mice.
abstract: Macrophage colony stimulating factor (M-CSF) is known to have profound effects upon vascular pathologies, but potential roles of other colony stimulating factors (CSF) are not well understood. We treated apo E deficient (apo E-/-) mice with granulocyte colony stimulating factor (G-CSF) or vehicle daily for 9 weeks, during which time they were fed a Western-style diet. G-CSF treatment resulted in increased proportions of circulating monocytes (6.9 ± 2.2% vs. 3.8 ± 0.3%; p < 0.05), a trend towards increased neutrophils (33.5 ± 19.1% vs. 22.2 ± 7.8%; p = 0.17), and decreased serum levels of total cholesterol (981 ± 594 vs. 1495 ± 1009 mg/dL; p < 0.005) compared to control mice. There was a trend towards less low density lipoprotein (LDL) in G-CSF treated mice (24.6 ± 2.4% vs. 37.4 ± 12.3%; p = 0.10). A greater proportion of bone marrow cells from G-CSF treated mice expressed membrane type 1 matrix metalloprotease (MT1-MMP) (G-CSF: 14.5 ± 5.5%;
  
  
  METHODS
  6.2 ± 5.0%; p < 0.05) compared to bone marrow cells from vehicle treated mice. G-CSF treatment was also associated with smaller atheromatous plaque, decreased Oil red O staining, and decreased infiltration of both Monocyte/Macrophage Marker Antibody (MOMA-2) and F4/80 dependent macrophage populations into aortic lesions. However, decreased plaque area appeared to be largely due to lower cholesterol levels in G-CSF-treated mice. Lesions in G-CSF treated mice appeared to be structurally distinct from control mice, containing relatively less lipid and macrophages. Our results suggest important roles for G-CSF in cholesterol metabolism, mobilization of bone marrow stem cells that might alter plaque development, and accumulation of lipids and macrophages into atherosclerotic lesions.
authors.affiliation: Cardiometabolic Research Unit, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science Los Angeles, CA.
authors.forename: Satyesh K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: The Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University Varanasi, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mishra
authors.affiliation: The Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University Varanasi, India.
authors.forename: Santosh
authors.initials: S
authors.lastname: Nagwani
authors.affiliation: Cardiometabolic Research Unit, Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science Los Angeles, CA ; The Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University Varanasi, India ; The Omics Biotechnology, Inc. Lawndale, CA.
authors.forename: Tripathi B
authors.initials: TB
authors.lastname: Rajavashisth
keywords: Atherosclerosis; G-CSF; apolipoprotein E; lipoproteins; macrophage; serum cholesterol