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. 2022 Sep 16;10(9):2303.
doi: 10.3390/biomedicines10092303.

Granulocyte Colony-Stimulating Factor Ameliorates Endothelial Activation and Thrombotic Diathesis Biomarkers in a Murine Model of Hind Limb Ischemia

Angeliki Valatsou  1 , Panagiotis Theofilis  1 , Spyridon Simantiris  1 , Georgia Vogiatzi  1   2 , Alexandros Briasoulis  3 , Marios Sagris  1 , Evangelos Oikonomou  1   2 , Alexios S Antonopoulos  1 , Alkistis Pantopoulou  4 , Narjes Nasiri-Ansari  4 , Elizabeth Fragopoulou  4 , Despoina Perrea  4 , Konstantinos Tsioufis  1 , Dimitris Tousoulis  1
Affiliations

Granulocyte Colony-Stimulating Factor Ameliorates Endothelial Activation and Thrombotic Diathesis Biomarkers in a Murine Model of Hind Limb Ischemia

Angeliki Valatsou et al. Biomedicines. .

Abstract

Novel therapies in peripheral arterial disease, such as granulocyte colony-stimulating factor (GCSF) administration, might result in anti-atherosclerotic effects. In this study, we used 10-week-old male ApoE-/- mice, which were fed an atherosclerosis-inducing diet for four weeks. At the end of the four weeks, hind limb ischemia was induced through left femoral artery ligation, the atherosclerosis-inducing diet was discontinued, and a normal diet was initiated. Mice were then randomized into a control group (intramuscular 0.4 mL normal saline 0.9% for 7 days) and a group in which GCSF was administrated intramuscularly in the left hind limb for 7 days (100 mg/kg). In the GCSF group, but not in the control group, we observed significant reductions in the soluble adhesion molecules (vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1)), sE-Selectin, and plasminogen activator inhibitor (PAI)-1 when they were measured through ELISA on the 1st and the 28th days after hind limb ischemia induction. Therefore, GCSF administration in an atherosclerotic mouse model of hind limb ischemia led to decreases in the biomarkers associated with endothelial activation and thrombosis. These findings warrant further validation in future preclinical studies.

Keywords: adhesion molecule; endothelium; granulocyte colony-stimulating factor; inflammation; limb ischemia; plasminogen activator inhibitor-1.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Differences in (A) soluble (s) E-Selectin, (B) s vascular cell adhesion molecule (VCAM)-1, and (C) s intercellular adhesion molecular (ICAM)-1 on 1st and 28th days after limb ischemia induction in the control and granulocyte colony-stimulating factor (GCSF) group.
Figure 2
Figure 2
Differences in plasminogen activator inhibitor (PAI)-1 on 1st and 28th days after limb ischemia induction in the control and granulocyte colony-stimulating factor (GCSF) groups.
See this image and copyright information in PMC

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