@article {1503143,
	title = {Long noncoding RNA  integrates a DNA-PK-mediated DNA damage response and vascular senescence},
	journal = {Sci Transl Med},
	volume = {12},
	number = {531},
	year = {2020},
	month = {2020 Feb 19},
	abstract = {Long noncoding RNAs (lncRNAs) are emerging regulators of biological processes in the vessel wall; however, their role in atherosclerosis remains poorly defined. We used RNA sequencing to profile lncRNAs derived specifically from the aortic intima of  mice on a high-cholesterol diet during lesion progression and regression phases. We found that the evolutionarily conserved lncRNA small nucleolar host gene-12 () is highly expressed in the vascular endothelium and decreases during lesion progression.  knockdown accelerated atherosclerotic lesion formation by 2.4-fold in  mice by increased DNA damage and senescence in the vascular endothelium, independent of effects on lipid profile or vessel wall inflammation. Conversely, intravenous delivery of  protected the tunica intima from DNA damage and atherosclerosis. LncRNA pulldown in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that  interacted with DNA-dependent protein kinase (DNA-PK), an important regulator of the DNA damage response. The absence of  reduced the DNA-PK interaction with its binding partners Ku70 and Ku80, abrogating DNA damage repair. Moreover, the anti-DNA damage agent nicotinamide riboside (NR), a clinical-grade small-molecule activator of NAD, fully rescued the increases in lesional DNA damage, senescence, and atherosclerosis mediated by  knockdown.  expression was also reduced in pig and human atherosclerotic specimens and correlated inversely with DNA damage and senescent markers. These findings reveal a role for this lncRNA in regulating DNA damage repair in the vessel wall and may have implications for chronic vascular disease states and aging.},
	issn = {1946-6242},
	doi = {10.1126/scitranslmed.aaw1868},
	author = {Haemmig, Stefan and Yang, Dafeng and Sun, Xinghui and Das, Debapria and Ghaffari, Siavash and Molinaro, Roberto and Chen, Lei and Deng, Yihuan and Freeman, Dan and Moullan, Norman and Tesmenitsky, Yevgenia and Wara, A K M Khyrul and Simion, Viorel and Shvartz, Eugenia and Lee, James F and Yang, Tianlun and Sukova, Galina and Marto, Jarrod A and Stone, Peter H and Lee, Warren L and Auwerx, Johan and Libby, Peter and Feinberg, Mark W}
}
