| First Author | Park JG | Year | 2016 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 36 |
| Issue | 9 | Pages | 1772-81 |
| PubMed ID | 27417587 | Mgi Jnum | J:246148 |
| Mgi Id | MGI:5920434 | Doi | 10.1161/ATVBAHA.116.307790 |
| Citation | Park JG, et al. (2016) Loss of Transcription Factor CREBH Accelerates Diet-Induced Atherosclerosis in Ldlr-/- Mice. Arterioscler Thromb Vasc Biol 36(9):1772-81 |
| abstractText | OBJECTIVE: Liver-enriched transcription factor cAMP-responsive element-binding protein H (CREBH) regulates plasma triglyceride clearance by inducing lipoprotein lipase cofactors, such as apolipoprotein A-IV (apoA-IV), apoA-V, and apoC-II. CREBH also regulates apoA-I transcription. This study aims to determine whether CREBH has a role in lipoprotein metabolism and development of atherosclerosis. APPROACH AND RESULTS: CREBH-deficient Creb3l3(-/-) mice were bred with Ldlr(-/-) mice creating Ldlr(-/-) Creb3l3(-/-) double knockout mice. Mice were fed on a high-fat and high-sucrose Western diet for 20 weeks. We showed that CREBH deletion in Ldlr(-/-) mice increased very low-density lipoprotein-associated triglyceride and cholesterol levels, consistent with the impairment of lipoprotein lipase-mediated triglyceride clearance in these mice. In contrast, high-density lipoprotein cholesterol levels were decreased in CREBH-deficient mice, which was associated with decreased production of apoA-I from the liver. The results indicate that CREBH directly activated Apoa1 gene transcription. Accompanied by the worsened atherogenic lipid profile, Ldlr(-/-) Creb3l3(-/-) mice developed significantly more atherosclerotic lesions in the aortas than Ldlr(-/-) mice. CONCLUSIONS: We identified CREBH as an important regulator of lipoprotein metabolism and suggest that increasing hepatic CREBH activity may be a novel strategy for prevention and treatment of atherosclerosis. |
