ANGIOTENSIN-CONVERTING ENZYME-INHIBITION PREVENTS ARTERIAL NUCLEAR FACTOR KAPPA-B ACTIVATION, MONOCYTE CHEMOATTRACTANT PROTEIN-1 EXPRESSION, AND MACROPHAGE INFILTRATION IN A RABBIT MODEL OF EARLY ACCELERATED ATHEROSCLEROSIS

Background The migration of monocytes into the vessel wall is a critic al event leading to the development of atherosclerosis. Monocyte chemo attractant protein-1 (MCP-1) is the main chemotactic factor involved i n this phenomenon, and nuclear factor-kappa B (NF-kappa B) is one of t he nuclear factors controlling its expression. ACE inhibitors have bee n useful in some experimental models of atherosclerosis. In this work, we addressed the hypothesis that angiotensin II (Ang II) may be impli cated in the recruitment of monocytes into the vessel wall through the activation of NF-kappa B and the induction of MCP-1 expression.Method s and Results Accelerated atherosclerosis was induced in the femoral a rteries of rabbits by endothelial desiccation and atherogenic diet for 7 days. Atherosclerotic vessels exhibited an increase in NF-kappa B-l ike activity, and p50 and p65 NF-kappa B subunits were identified as c omponents of this activity. MCP-1 (mRNA and protein) was also expresse d in the injured vessels coincidently with the neointimal macrophage i nfiltration. ACE inhibition with quinapril reduced these three paramet ers. In cultured monocytic and vascular smooth muscle cells, Ang II el icited an increase in NF-kappa B activation and MCP-1 expression that was prevented by preincubation of cells with pyrrolidinedithiocarbamat e, an inhibitor of NF-kappa B activation. Conclusions The present data support a role for Ang II in neointimal monocyte infiltration through NF-kappa B activation and MCP-1 expression in a model of accelerated atherosclerosis in rabbits. Our results suggest that ACE inhibitors ma p have a beneficial effect in early atherosclerosis.