© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits
aDepartment of Cardiology, University of Amsterdam, Amsterdam, The Netherlands
bDepartment of Cardiology, University of Freiburg, Freiburg, Germany
cDepartment of Experimental Cardiology, Max Planck Institute, Bad Nauheim, Germany
* Corresponding author. Tel.: +49-761-270-6349; fax: +49-761-503-4950. vanroyen{at}med1.ukl.uni-freiburg.de
Objective: The objective of our study was to quantify the arteriogenic potency of Monocyte Chemoattractant Protein-1 (MCP-1) under hyperlipidemic conditions. Additionally, we aimed to determine the effects of locally applied MCP-1 on systemic serum lipid levels as well as on atherosclerosis. Methods: A total of sixty-four Watanabe rabbits was treated with either low dose MCP-1 (1 µg/kg/week), high dose MCP-1 (3.3 µg/kg/week) or PBS as a control substance. Substances were applied directly into the collateral circulation via an osmotic minipump with the catheter placed in the proximal stump of the ligated femoral artery. Either 1 week or 6 months after initiation of the treatment X-ray angiography was performed as well as measurements of collateral conductance using fluorescent microspheres. The extent of atherosclerosis was quantified in whole aortas using Sudan IV staining. Results: One week after ligation of the femoral artery a significant increase in collateral conductance was observed in animals treated with high dose MCP-1 (control: 2.2±0.8 ml/min/100 mmHg vs. MCP-1 high dose: 8.9±2.0 ml/min/100 mmHg, P<0.05). Six months after femoral artery ligation no differences were found between the treated and the control group (PBS; 44.9±11.6 ml/min/100 mmHg, MCP-1; 47.8±11.5 ml/min/100 mmHg, P = NS). No influence was found on serum lipids or on the development of atherosclerosis in the present model. Conclusion: MCP-1 accelerates arteriogenesis upon femoral artery ligation under hyperlipidemic conditions. Six months after treatment these pro-arteriogenic effects of MCP-1 can no longer be observed. The present data do not show an effect of local MCP-1 treatment on serum lipids or on atherosclerosis. It should be noted however that a high standard deviation was observed for the data on atherosclerotic surface area, necessitating additional experiments in a different model of atherosclerosis.
KEYWORDS Atherosclerosis; Collateral circulation; Cytokines; Hemodynamics; Macrophages
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