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(Circulation. 1997;96:2514-2519.)
© 1997 American Heart Association, Inc.

Articles

Apolipoprotein(a) Induces Monocyte Chemotactic Activity in Human Vascular Endothelial Cells

Michael Poon, MD; Xiaoxia Zhang, MD, PhD; Kevin G. Dunsky, MD; Mark B. Taubman, MD; ; Peter C. Harpel, MD

From the Cardiovascular Institute (M.P., K.G.D., M.B.T.) and the Division of Hematology (X.Z., P.C.H.), Department of Medicine, and the Brookdale Center for Molecular Biology (M.B.T.), Mount Sinai School of Medicine, New York, NY.

Correspondence to Michael Poon, MD, Box 1030, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029. E-mail mpoon{at}smtplink.mssm.edu

Background Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis.

Methods and Results This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony–stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a).

Conclusions These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.

Key Words: lipoproteins • atherosclerosis

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