PMID- 12504827 OWN - NLM STAT- MEDLINE DCOM- 20030429 LR - 20190513 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 57 IP - 1 DP - 2003 Jan TI - Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits. PG - 178-85 AB - 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 microg/kg/week), high dose MCP-1 (3.3 microg/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. FAU - van Royen, N AU - van Royen N AD - Department of Cardiology, University of Amsterdam, Amsterdam, The Netherlands. vanroyen@med1.ukl.uni-freiburg.de FAU - Hoefer, I AU - Hoefer I FAU - Buschmann, I AU - Buschmann I FAU - Kostin, S AU - Kostin S FAU - Voskuil, M AU - Voskuil M FAU - Bode, Ch AU - Bode Ch FAU - Schaper, W AU - Schaper W FAU - Piek, J J AU - Piek JJ LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Chemokine CCL2) RN - 0 (Lipids) SB - IM MH - Animals MH - Arteriosclerosis MH - Chemokine CCL2/*therapeutic use MH - *Collateral Circulation MH - *Femoral Artery/diagnostic imaging MH - Hyperlipidemias/blood/diagnostic imaging/*drug therapy MH - Ligation MH - Lipids/blood MH - Models, Animal MH - Rabbits MH - Radiography EDAT- 2002/12/31 04:00 MHDA- 2003/04/30 05:00 CRDT- 2002/12/31 04:00 PHST- 2002/12/31 04:00 [pubmed] PHST- 2003/04/30 05:00 [medline] PHST- 2002/12/31 04:00 [entrez] AID - S0008636302006156 [pii] AID - 10.1016/s0008-6363(02)00615-6 [doi] PST - ppublish SO - Cardiovasc Res. 2003 Jan;57(1):178-85. doi: 10.1016/s0008-6363(02)00615-6.