title: Oxygenized low density lipoprotein down-regulates the TRPV4 protein expression of macrophage through activation of peroxisome proliferator-activated receptor γ.
abstract: BACKGROUND
  TRPV4, a non-selective cation channel, is involved in lipometabolism and atherosclerosis. However, whether TRPV4 participates in oxygenized low density lipoprotein (oxLDL)-induced foam cell formation remains unknown. The present study investigates the effect of oxLDL on the expression of TRPV4 in macrophages and its underlying mechanisms.
  
  
  METHODS
  The expression of TRPV4 in RAW264.7 and phorbol-12-myristate-13-acetate (PMA) induced U937, THP-1 cells was detected by immunofluorescence, and western blot was used to detect the TRPV4 expression before and after PMA induction. Each cell line was divided into three groups, including control group, native low-density lipoprotein (nLDL) (100 μg/mL) group and oxLDL (100μg/mL) group; the expression of TRPV4 in each group was measured using immunohistochemistry and western blot. TRPV4 protein expression was detected by western blot after RAW 264.7 cells were treated with 0, 0.01 μM, 0.1 μM and 1 μM T0070907 or preincubated with 0.1 μM T0070709 for 1 h before incubation with oxLDL for 24 h.
  
  
  RESULTS
  In all macrophage cell lines, TRPV4 was widely expressed. PMA increased TRPV4 expression in U937 and THP-1 cells. There was no significant difference in TRPV4 expression in the nLDL group compared to that in the control group; however a significant reduction in TRPV4 expression was detected in the oxLDL group compared to that in the control and nLDL groups using measurements obtained from both immunohistochemistry and western blot. The PPARγ inhibitor T0070907 enhanced the basal expression of TRPV4 and protected RAW264.7 cells from oxLDL-induced TRPV4 down-regulation.
  
  
  CONCLUSIONS
  This study revealed that TRPV4 was widely expressed in macrophages and that oxLDL could induce the down-regulation of TRPV4 expression through its actions on PPARγ. This study may serve as an important first step for further investigation into the roles of TRPV4 in macrophage-derived foam cell formation in atherosclerosis.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xue
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Urology Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China - zhaojinping33@hotmail.com.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D018955:CD36 Antigens / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D047494:PPAR delta / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D001549:Benzamides; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D047494:PPAR delta; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; C099252:oxidized low density lipoprotein; D013755:Tetradecanoylphorbol Acetate