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(Circulation Research. 2006;98:378.)
© 2006 American Heart Association, Inc.

Molecular Medicine

LPP Expression During In Vitro Smooth Muscle Differentiation and Stent-Induced Vascular Injury

I. Gorenne^*, L. Jin^*, T. Yoshida, J.M. Sanders, I.J. Sarembock, G.K. Owens, A.P. Somlyo, A.V. Somlyo

From the Department of Molecular Physiology and Biological Physics (I.G., L.J., T.Y., G.K.O., A.P.S., A.V.S.), Department of Medicine (J.M.S., I.J.S.), and Cardiovascular Research Center (T.Y., G.K.O., A.V.S.), University of Virginia, Charlottesville, Va.

Correspondence to Avril V. Somlyo, PhD, PO Box 800736, Charlottesville, VA 22908. E-mail avs5u{at}virginia.edu

Lipoma preferred partner (LPP) has been identified as a protein highly expressed in smooth muscle (SM) tissues. The aim of the present study was to determine mechanisms that regulate LPP expression in an in vitro model of SM cell (SMC) differentiation and in stent-induced pig coronary vessel injury. All trans-retinoic acid treatment of A404 cells induced a strong increase in LPP, as well as SM -actin, SM myosin heavy chain, and smoothelin mRNA levels, in a Rho kinase (ROK)-dependent manner. Adenovirus mediated overexpression of myocardin in A404 cells significantly increased LPP mRNA expression. Interestingly, inactivation of RhoA with C3-exoenzyme or treatment with ROK inhibitors strongly inhibited myocardin mRNA expression in retinoic acid–treated A404 cells or human iliac vein SMCs. LPP silencing with short interfering RNA significantly decreased SMC migration. LPP expression was also markedly decreased in focal adhesion kinase (FAK)-null cells known to have impaired migration but rescued with inducible expression of FAK. LPP expression in FAK-null fibroblasts enhanced cell spreading. In stented pig coronary vessels, LPP was expressed in the neointima of cells lacking smoothelin and showed expression patterns identical to those of SM -actin. In conclusion, LPP appears to be a myocardin-, RhoA/ROK-dependent SMC differentiation marker that plays a role in regulating SMC migration.

Key Words: lipoma preferred partner • smooth muscle • vascular injury • cell migration • focal adhesion kinase

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