title: Loss of Transcription Factor CREBH Accelerates Diet-Induced Atherosclerosis in Ldlr-/- Mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Jong-Gil
authors.initials: JG
authors.lastname: Park
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
authors.forename: Sungyun
authors.initials: S
authors.lastname: Cho
authors.affiliation: From the Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY. anl2042@med.cornell.edu.
authors.forename: Ann-Hwee
authors.initials: AH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D045744:Cell Line, Tumor; D008076:Cholesterol, HDL / Q000097:blood; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency* / Q000235:genetics; D059305:Diet, High-Fat; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D012720:Severity of Illness Index; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014280:Triglycerides / Q000097:blood
chemical_list: C415826:Apob protein, mouse; D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D019422:Dietary Sucrose; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D008071:Lipoprotein Lipase
keywords: apolipoprotein; atherosclerosis; cholesterol; transcription factors; triglycerides