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(Circulation Research. 2009;104:1139.)
© 2009 American Heart Association, Inc.

Editorials

H-RAS Controls Phenotypic Profiles of Vascular Smooth Muscle Cells and the Pathogenesis of Vascular Proliferative Disorders

Kenneth S. Ramos

From the Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY 40202.

Correspondence to K.S. Ramos, Delia Baxter Research Building, Room 227, Louisville, KY 40202. E-mail kenneth.ramos@louisville.edu

See related article, pages 1192–1200

Key Words: H-RAS • vascular smooth muscle cell differentiation • vascular smooth muscle cell phenotypes • vascular smooth muscle cell proliferation • vascular proliferative disorders

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Vascular smooth muscle (VSMC) migration, proliferation, and hypertrophy following physical, chemical, or biological injury are key events in the onset and progression of vascular proliferative disorders, such as atherosclerosis, postangioplasty stenosis, venous bypass graft failure, and transplantation. Under normal conditions, VSMCs exist in a quiescent state of growth that supports contractile function and structural and functional integrity of the vascular wall. Vascular injury disrupts critical cell-cell and cell-matrix interactions, leading to activation of VSMCs. The activated VSMC phenotype is characterized by gradual loss of differentiated characteristics, increased response to chemotactic agents, and uncontrolled proliferation. Not surprisingly, the quest for molecular triggers of VSMC proliferation led investigators to studies of cell cycle control proteins and mitogenic signaling within the vascular wall. Of note are seminal studies examining the signaling cascades of platelet-derived growth factor^1,2 and various protooncogenes, including myb,^3,4 myc,^5,6 and H-ras.^7,8 H-RAS quickly emerged as a critical convergence point in VSMC mitogenic signaling and was identified as a putative target for pharmacological intervention in vascular proliferative disorders.⁹

H- and K-ras were first identified as viral oncogenes in Harvey and Kirsten rat sarcomas, respectively.¹⁰ Subsequent studies identified a third member, N-ras, as a protooncogene present in various tumor cell lines.¹¹ Studies of the cellular viral ras oncogene counterparts led to the identification of ras protooncogenes as TATA-less, GC-rich genes that encode for 21-kDa proteins with homology to the subunit of G proteins.¹² p21^RAS binds guanine nucleotides and possesses intrinsic GTPase activity,¹³ and . . . [Full Text of this Article]