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(Circulation Research. 2004;95:179.)
© 2004 American Heart Association, Inc.

Cellular Biology

Apolipoprotein D and Platelet-Derived Growth Factor-BB Synergism Mediates Vascular Smooth Muscle Cell Migration

Wesley C.Y. Leung, Allan Lawrie, Sandra Demaries, Hamid Massaeli, Andrea Burry, Shmuel Yablonsky, Jennifer M. Sarjeant, Euridiki Fera, Eric Rassart, J. Geoffrey Pickering, Marlene Rabinovitch

From the Cardiovascular Research Program, Research Institute, The Hospital for Sick Children, and the Departments of Pediatrics, Laboratory Medicine, and Pathobiology, and Medicine (W.C.Y.L., S.D., H.M., A.B., S.Y., J.M.S., M.R.), University of Toronto; Department of Biological Sciences, Université du Québec à Montréal (E.R.), Montreal; and the Robarts Research Institute (E.F., J.G.P.), University of Western Ontario, Canada. Present address for A.L. and M.R. is Stanford University School of Medicine, Stanford, Calif, and A.L. worked on this study at Stanford University.

Correspondence to Dr Marlene Rabinovitch, Stanford University School of Medicine, CCSR-2245B, 269 Campus Dr, Stanford, CA 94305-5162. E-mail marlener{at}stanford.edu

We identified apolipoprotein (apo)D in a search for proteins upregulated in a posttranscriptional manner similar to fibronectin in motile smooth muscle cells (SMCs). To address the function of apoD in SMCs, we cloned a partial apoD cDNA from ovine aortic (Ao) SMCs using RT-PCR. We documented a 2.5-fold increase in apoD protein but no increase in apoD mRNA in Ao SMCs 48 hours after a multiwound migration assay (P<0.01). Confocal microscopy revealed prominent perinuclear and trailing edge expression of apoD in migrating SMCs but not in the confluent monolayer. Stimulation of Ao SMCs with 10 ng/mL platelet-derived growth factor (PDGF)-BB increased apoD protein expression (P<0.05). Moreover, PDGF-BB–stimulated migration of human pulmonary artery SMCs was suppressed by knock-down of apoD using RNAi. Stable overexpression of apoD in Ao SMCs cultured in 10% fetal bovine serum promoted random migration by 62% compared with vector-transfected cells (P<0.01). Overexpression of apoD or addition of exogenous apoD to a rat aortic SMC line (A10) stimulated their migration in response to a subthreshold dose of PDGF-BB (P<0.05). This was unrelated to increased phosphorylation of ERK1/2 or of phospholipase C-1, but correlated with enhanced Rac1 activation. This study shows that apoD can be expressed or taken up by SMCs and can regulate their motility in response to growth factors.

Key Words: vascular smooth muscle • apolipoprotein D • cell migration • platelet-derived growth factor • Rac1

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