Article

Ribosomal Protein L17, RpL17, is an Inhibitor of Vascular Smooth Muscle Growth and Carotid Intima Formation

University of Rochester School of Medicine & Dentistry, Rochester, NY.
Circulation (Impact Factor: 14.95). 10/2012; 126(20). DOI: 10.1161/CIRCULATIONAHA.112.125971
Source: PubMed

ABSTRACT BACKGROUND: Carotid intima-media thickening is associated with increased cardiovascular risk in humans. We discovered that intima formation and cell proliferation in response to carotid injury is greater in SJL/J (SJL) compared to C3HeB/FeJ (C3H/F) mice. The purpose of this study was to identify candidate genes contributing to intima formation. METHODS AND RESULTS: We performed microarray and bioinformatic analyses of carotid arteries from C3H/F and SJL mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the ribosome pathway was significantly up-regulated in C3H/F compared to SJL. Expression of a ribosomal protein, RpL17, was >40-fold higher in C3H/F carotids compared to SJL. Aortic vascular smooth muscle cells (VSMC) from C3H/F grew slower compared to SJL. To determine the role of RpL17 in VSMC growth regulation we analyzed the relationship between RpL17 expression and cell cycle progression. Cultured VSMC from mouse, rat, and human showed that RpL17 expression inversely correlated with growth as shown by decreased cells in S phase and increased cells in G(0)/G(1). To prove that RpL17 acted as a growth inhibitor in vivo we used pluronic gel delivery of RpL17 siRNA to C3H/F carotid arteries. This resulted in an 8-fold increase in the number of proliferating cells. Furthermore, following partial carotid ligation in SJL mice, RpL17 expression in the intima and media decreased while the number of proliferating cells increased. CONCLUSIONS: RpL17 acts as a VSMC growth inhibitor (akin to a tumor suppressor) and represents a potential therapeutic target to limit carotid intima-media thickening.

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