title: 3,3'-Diindolylmethane protects against cardiac hypertrophy via 5'-adenosine monophosphate-activated protein kinase-α2.
abstract: OBJECTIVE
  3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. It has strong antioxidant and anti-angiogenic effects and promotes the apoptosis of a variety of tumor cells. However, little is known about the critical role of DIM on cardiac hypertrophy. In the present study, we investigated the effects of DIM on cardiac hypertrophy.
  
  
  METHODS
  Multiple molecular techniques such as Western blot analysis, real-time PCR to determine RNA expression levels of hypertrophic, fibrotic and oxidative stress markers, and histological analysis including H&E for histopathology, PSR for collagen deposition, WGA for myocyte cross-sectional area, and immunohistochemical staining for protein expression were used.
  
  
  RESULTS
  In pre-treatment and reverse experiments, C57/BL6 mouse chow containing 0.05% DIM (dose 100 mg/kg/d DIM) was administered one week prior to surgery or one week after surgery, respectively, and continued for 8 weeks after surgery. In both experiments, DIM reduced to cardiac hypertrophy and fibrosis induced by aortic banding through the activation of 5'-adenosine monophosphate-activated protein kinase-α2 (AMPKα2) and inhibition of mammalian target of the rapamycin (mTOR) signaling pathway. Furthermore, DIM protected against cardiac oxidative stress by regulating expression of estrogen-related receptor-alpha (ERRα) and NRF2 etc. The cardioprotective effects of DIM were ablated in mice lacking functional AMPKα2.
  
  
  CONCLUSIONS
  DIM significantly improves left ventricular function via the activation of AMPKα2 in a murine model of cardiac hypertrophy.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Jing
authors: J
authors: Zong
authors: Wei
authors: W
authors: Deng
authors: Heng
authors: H
authors: Zhou
authors: Zhou-yan
authors: ZY
authors: Bian
authors: Jia
authors: J
authors: Dai
authors: Yuan
authors: Y
authors: Yuan
authors: Jie-yu
authors: JY
authors: Zhang
authors: Rui
authors: R
authors: Zhang
authors: Yan
authors: Y
authors: Zhang
authors: Qing-qing
authors: QQ
authors: Wu
authors: Hai-peng
authors: HP
authors: Guo
authors: Hong-liang
authors: HL
authors: Li
authors: Qi-zhu
authors: QZ
authors: Tang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D007211:Indoles; C534978:Prkaa2 protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C016392:3,3'-diindolylmethane