© 1999 American Heart Association, Inc.
Original Contribution |
EVEC, a Novel Epidermal Growth Factor–Like Repeat-Containing Protein Upregulated in Embryonic and Diseased Adult Vasculature
From the Departments of Internal Medicine (R.C.K.), Molecular Biology and Oncology (R.C.K., E.N.O.), and Pathology (J.A.R.), University of Texas Southwestern Medical Center, Dallas, Tex, and Department of Physiology (J.M.M.), Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wis.
Correspondence to Eric N. Olson, Chairman, Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9148. E-mail eolson{at}hamon.swmed.edu
Abstract—A hallmark of vascular lesions is the phenotypic modulation of vascular smooth muscle cells (VSMCs) from a quiescent, contractile state to a more primitive, proliferative phenotype with a more fetal pattern of gene expression. Using subtraction hybridization to identify genes that may regulate this transition, we cloned a novel gene named EVEC, an acronym for its expression in the embryonic vasculature and the presence of Ca2+ binding epidermal growth factor–like repeats contained in the predicted protein structure. Although these repeats are characteristic of the extracellular matrix proteins, fibrillin, fibulin, and the latent transforming growth factor-ß binding proteins, EVEC most closely resembles the H411 and T16/S1-5 gene products, the latter of which are believed to regulate DNA synthesis in quiescent fibroblasts. Using in situ hybridization, we demonstrated that EVEC is expressed predominantly in the VSMCs of developing arteries in E11.5 through E16.5 mouse embryos. Lower levels of expression are also observed in endothelial cells, perichondrium, intestine, and mesenchyme of the face and kidney. EVEC mRNA expression is dramatically downregulated in adult arteries, except in the uterus, where cyclic angiogenesis continues; however, EVEC expression is reactivated in 2 independent rodent models of vascular injury. EVEC mRNA is observed in cellular elements of atherosclerotic plaques of LDL receptor–deficient, human apolipoprotein B transgenic mice and in VSMCs of the media and neointima of balloon-injured rat carotid arteries. These data suggest that EVEC may play an important role in the regulation of vascular growth and maturation during development and in lesions of injured vessels.
Key Words: EVEC • vascular smooth muscle cell • atherosclerosis • restenosis
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