Long noncoding RNA SNHG12 integrates a DNA-PK-mediated DNA damage response and fascular senescence

Haemmig S, Yang D, Sun X, Das D, Ghaffari S, Molinaro R, Chen L, Deng Y, Freeman D, Moullan N, Tesmenitsky Y, Wara AKMK, Simion V, Shvartz E, Lee JF, Yang T, Sukova G, Marto JA, Stone PH, Lee WL, Auwerx J, Libby P, Feinberg MW

DNA damage and senescence are thought to enhance atherosclerotic lesion formation, although how this happens is unclear. Haemmig et al. identified an endothelial-enriched long noncoding RNA (lncRNA) as a DNA-dependent protein kinase (DNA-PK)–dependent regulator of vascular DNA damage and cellular senescence. Small nucleolar host gene-12 (SNHG12) was down-regulated in mouse, pig, and human atherosclerotic arteries and correlated with DNA damage and senescence. Endothelial Snhg12 knockdown exacerbated vascular cellular senescence and lesion formation in mouse models of atherosclerosis. Both nicotinamide riboside administration and intravenous delivery of Snhg12 rescued disease progression in vivo, suggesting potential to combat atherosclerosis by targeting a mechanism of vascular senescence.

Journal

Science Translational Medicine

Model

TBD

Impact Factor

16.710

Preclinical Research, VitalityANAD Staff