PMID- 11023981 OWN - NLM STAT- MEDLINE DCOM- 20001108 LR - 20131121 IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 14 IP - 13 DP - 2000 Oct TI - Anti-monocyte chemoattractant protein-1 gene therapy inhibits vascular remodeling in rats: blockade of MCP-1 activity after intramuscular transfer of a mutant gene inhibits vascular remodeling induced by chronic blockade of NO synthesis. PG - 1974-8 AB - Monocyte chemoattractant protein-1 (MCP-1) may play an essential part in the formation of arteriosclerosis by recruiting monocytes into the arterial wall. Thus, we devised a new strategy for anti-MCP-1 gene therapy against arteriosclerosis by transfecting an amino-terminal deletion mutant (missing the amino-terminal amino acids 2 to 8) of the human MCP-1 gene into a remote organ (skeletal muscles). Intramuscular transduction with the mutant MCP-1 gene blocked monocyte recruitment induced by a subcutaneous injection of recombinant MCP-1. In a rat model in which the chronic inhibition of endothelial nitric oxide synthesis induces early vascular inflammation as well as subsequent coronary vascular remodeling, this strategy suppressed monocyte recruitment into the coronary vessels and the development of vascular medial thickening, but did not reduce perivascular fibrosis. Thus, MCP-1 is necessary for the development of medial thickening but not for fibrosis in this model. This new strategy may be a useful and feasible gene therapy against arteriosclerosis. FAU - Egashira, K AU - Egashira K AD - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. egashira@cardiol.med.kyushu-u.ac.jp FAU - Koyanagi, M AU - Koyanagi M FAU - Kitamoto, S AU - Kitamoto S FAU - Ni, W AU - Ni W FAU - Kataoka, C AU - Kataoka C FAU - Morishita, R AU - Morishita R FAU - Kaneda, Y AU - Kaneda Y FAU - Akiyama, C AU - Akiyama C FAU - Nishida, K I AU - Nishida KI FAU - Sueishi, K AU - Sueishi K FAU - Takeshita, A AU - Takeshita A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Chemokine CCL2) RN - 0 (Recombinant Proteins) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos3 protein, rat) SB - IM MH - Animals MH - Arteriosclerosis/*therapy MH - Chemokine CCL2/administration & dosage/*antagonists & inhibitors/genetics MH - Chemotaxis, Leukocyte MH - Coronary Vessels/drug effects MH - Dermis MH - Genetic Therapy/*methods MH - Injections, Intramuscular MH - Male MH - Monocytes/physiology MH - Muscle, Skeletal/metabolism MH - Mutation MH - Nitric Oxide MH - Nitric Oxide Synthase MH - Nitric Oxide Synthase Type III MH - Rats MH - Rats, Inbred WKY MH - Recombinant Proteins/administration & dosage EDAT- 2000/10/12 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/10/12 11:00 PHST- 2000/10/12 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/12 11:00 [entrez] AID - 14/13/1974 [pii] AID - 10.1096/fj.00-0141com [doi] PST - ppublish SO - FASEB J. 2000 Oct;14(13):1974-8. doi: 10.1096/fj.00-0141com.