title: CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC.
abstract: ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Japan.
authors.forename: Ada
authors.initials: A
authors.lastname: Congrains
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Osamu
authors.initials: O
authors.lastname: Yasuda
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Oguro
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D050197:Atherosclerosis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012326:RNA Splicing; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated