Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits

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, <F>P<0.05</F>). 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. [Copyright &y& Elsevier]