title: Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.
abstract: Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism.
  
  
  
  Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting.
  
  
  
  Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis.
  
  
  
  These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.
authors.affiliation: aHeart Research Center of Chonnam National University Hospital, Gwangju, Republic of Korea bJilin Hospital Affiliated with Jilin University, Jilin cYanbian University Hospital, Jilin Yanbian dThe Second Hospital of Jilin University, Changchun, China *Li Jin and Ming Quan Lin contributed equally to the article.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Ming Quan
authors.initials: MQ
authors.lastname: Lin
authors.forename: Zhe Hao
authors.initials: ZH
authors.lastname: Piao
authors.forename: Jae Yeong
authors.initials: JY
authors.lastname: Cho
authors.forename: Gwi Ran
authors.initials: GR
authors.lastname: Kim
authors.forename: Sin Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Yuhee
authors.initials: Y
authors.lastname: Ryu
authors.forename: Simei
authors.initials: S
authors.lastname: Sun
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005707:Gallic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000503:physiopathology; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D005707:Gallic Acid; D019001:Nitric Oxide Synthase; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D019331:NG-Nitroarginine Methyl Ester