(Circulation. 1997;95:1532-1541.)
© 1997 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme Inhibition Prevents Arterial Nuclear Factor-
B Activation, Monocyte Chemoattractant Protein-1 Expression, and Macrophage Infiltration in a Rabbit Model of Early Accelerated Atherosclerosis
From the Research Laboratory (M.H.-P., C.B., M.O., M.R.-O., J.E.), Division of Cardiology (J.T.), and Department of Pathology (G.R.), Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
Correspondence to Jesús Egido, MD, Research Laboratories, Fundación Jiménez Díaz, Avda Reyes Católicos 2, 28040 Madrid, Spain. E-mail egido{at}alpha2.ft.uam.es
Background The migration of monocytes into the vessel wall is
a critical event leading to the development of atherosclerosis.
Monocyte chemoattractant protein-1 (MCP-1) is the main chemotactic
factor involved in this phenomenon, and nuclear factor-
B (NF-B)
is one of the nuclear factors controlling its expression. ACE
inhibitors have been useful in some experimental models of
atherosclerosis. In this work, we addressed the hypothesis that
angiotensin II (Ang II) may be implicated in the recruitment of
monocytes into the vessel wall through the activation of NF-B and
the induction of MCP-1 expression.
Methods and Results Accelerated atherosclerosis was induced
in the femoral arteries of rabbits by endothelial desiccation and
atherogenic diet for 7 days. Atherosclerotic vessels exhibited an
increase in NF-B–like activity, and p50 and p65 NF-B subunits
were identified as components of this activity. MCP-1 (mRNA and
protein) was also expressed in the injured vessels coincidently with
the neointimal macrophage infiltration. ACE inhibition with quinapril
reduced these three parameters. In cultured monocytic and vascular
smooth muscle cells, Ang II elicited an increase in NF-B activation
and MCP-1 expression that was prevented by preincubation of cells with
pyrrolidinedithiocarbamate, an inhibitor of NF-B activation.
Conclusions The present data support a role for Ang II in
neointimal monocyte infiltration through NF-B activation and MCP-1
expression in a model of accelerated atherosclerosis in rabbits. Our
results suggest that ACE inhibitors may have a beneficial effect in
early atherosclerosis.
Key Words: angiotensin • atherosclerosis • molecular biology • immunohistochemistry
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