EVEC, a novel epidermal growth factor-like repeat-containing protein upregulated in embryonic and diseased adult vasculature.
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-beta 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.
Kowal
R C
RC
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9148, USA.
Richardson
J A
JA
Miano
J M
JM
Olson
E N
EN
D000367:Age Factors; D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D019556:COS Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000378:metabolism; D004549:Elastin / Q000032:analysis; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D005333:Fetus / Q000737:chemistry / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D017539:Tunica Intima / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; C120769:Fbln5 protein, mouse; C492372:Fbln5 protein, rat; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D004549:Elastin