title: Dihydrocapsaicin Attenuates Plaque Formation through a PPARγ/LXRα Pathway in apoE(-/-) Mice Fed a High-Fat/High-Cholesterol Diet.
abstract: Atherosclerosis is a chronic inflammatory disease and represents the major cause of cardiovascular morbidity and mortality. There is evidence that dihydrocapsaicin (DHC) can exert multiple pharmacological and physiological effects. Here, we explored the effect of DHC in atherosclerotic plaque progression in apoE(-/-) mice fed a high-fat/high-cholesterol diet.
  
  
  
  apoE(-/-) mice were randomly divided into two groups and fed a high-fat/high-cholesterol diet with or without DHC for 12 weeks. We demonstrated that cellular cholesterol content was significantly decreased while apoA1-mediated cholesterol efflux was significantly increased following treatment with DHC in THP-1 macrophage-derived foam cells. We also observed that plasma levels of TG, LDL-C, VLDL-C, IL-1β, IL-6, TNF-α and CRP were markedly decreased while plasma levels of apoA1 and HDL-C were significantly increased, and consistent with this, atherosclerotic lesion development was significantly inhibited by DHC treatment of apoE(-/-) mice fed a high-fat/high-cholesterol diet. Moreover, treatment with both LXRα siRNA and PPARγ siRNA made the up-regulation of DHC on ABCA1, ABCG1, ABCG5, SR-B1, NPC1, CD36, LDLR, HMGCR, apoA1 and apoE expression notably abolished while made the down-regulation of DHC on SRA1 expression markedly compensated. And treatment with PPARγ siRNA made the DHC-induced up-regulation of LXRα expression notably abolished while treatment with LXRα siRNA had no effect on DHC-induced PPARγ expression.
  
  
  
  These observations provide direct evidence that DHC can significantly decrease atherosclerotic plaque formation involving in a PPARγ/LXRα pathway and thus DHC may represent a promising candidate for a therapeutic agent for the treatment or prevention of atherosclerosis.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Huang
authors.forename: Xin-Ru
authors.initials: XR
authors.lastname: Mao
authors.forename: Jun-Yao
authors.initials: JY
authors.lastname: Yang
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002791:Cholesterol, Dietary / Q000009:adverse effects* / Q000097:blood; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D016207:Cytokines; D000071518:Liver X Receptors; D047495:PPAR gamma; D002211:Capsaicin; C012906:dihydrocapsaicin