Abstract :The chromosome 9p21 region is the strongest susceptibility locus for Cardiovascular Disease
(CVD) and a hot-spot for multiple disease-associated polymorphisms. The locus encodes for a long
non-coding RNA, ANRIL. The disease-associated variants in the region have been correlated with
ANRIL expression, suggesting ANRIL mediates these associations.
Since most of diseases associated with the locus are common diseases of aging, we sought to
investigate the relation between ANRIL expression and age. We measured ANRIL expression by
RT-PCR in three groups: 70 years-old, 80 years-old and 90 years-old subjects. ANRIL expression
increased dramatically between 70 to 80 years-old.
In addition, we profiled the regulatory effects of ANRIL knock-down in endothelial cells. The
artificial depletion of ANRIL caused the down-regulation of an upstream regulator of senescence,
IL1A, and other inflammatory genes. Conversely, it produced the up-regulation of the transcription
factor KLF2, which has athero-protective properties.
Our results suggest ANRIL has a pro-atherogenic effect by inducing inflammatory and senescencerelated
molecules in endothelial cells. Aggravated senescence and inflammation are characteristic
of aging and might be mediated by the age-related changes in ANRIL expression. ANRIL is a
promising target for future therapies for many aging-related diseases.