The role of long noncoding RNA Nron in atherosclerosis development and plaque stability

The major clinical consequences of atherosclerosis such as myocardial infarction or stroke are because of thrombotic events associated with acute rupture or erosion of an unstable plaque. Here, we identify an lncRNA Noncoding Repressor of NFAT (Nron) as a critical regulator of atherosclerotic plaque stability. Nron overexpression (OE) in vascular smooth muscle cells (VSMC) induces a highly characteristic architecture of more-vulnerable plaques, while Nron knockdown (KD) suppresses the development of atherosclerosis and favors plaque stability. Mech-anistically, Nron specifically binds to and negatively regulates NFATc3, thus inhibiting the proliferation and promoting the apoptosis of VSMCs. Moreover, we also provide evidence that Nron increases the production and secretion of VEGFA from VSMCs, which functions as a paracrine factor to enhance intra-plaque angiogenesis. All of these effects contribute to plaque instability. Genetic or pharmacological inhibition of Nron may have potential for future therapy of atherosclerosis.

Automated summary

Atherosclerosis is characterized by the rupture or erosion of unstable plaques, leading to thrombotic events such as myocardial infarction or stroke. In this study, researchers identified a long noncoding RNA called Noncoding Repressor of NFAT (Nron) as a critical regulator of plaque stability in atherosclerosis. Overexpression of Nron led to the formation of more vulnerable plaques, while knockout of Nron inhibited atherosclerosis development and promoted plaque stability. Mechanistically, Nron bound to and negatively regulated NFATc3, which inhibited the proliferation and promoted the apoptosis of vascular smooth muscle cells. Additionally, Nron increased the production and secretion of VEGFA from these cells, enhancing intra-plaque angiogenesis. Inhibition of Nron may hold potential as a therapeutic strategy for atherosclerosis.