Hepatic HuR protects against atherosclerosis through bile acid production

However, if this phenotype further impacts the development of atherosclerosis (AS) remains to be studied. Here, we report that HuR represses the production of chenodeoxycholic acid (CDCA) and taurocholic acid (TCA) in the liver through repressing the expression of CYP7A1, the rate-limiting enzyme for the central pathway of BA production.

HuR destabilizes Cyp7a1 mRNA by associating with its 3’UTR. In response to high-cholesterol diet (HCD), hepatic HuR increases the expression of CYP7A1 in the liver, thereby increasing the levels of CDCA and TCA in the liver and serum, activating HuR-PSPF (platelet-secreted pro-inflammatory factors) regulatory process, and aggravating HCD-induced AS in APOE (-/-) mice. Administration of TCA and CDCA activates HuR-PSPF regulatory process and at the same time aggravates HCD-induced AS.