title: Pyridostigmine ameliorates cardiac remodeling induced by myocardial infarction via inhibition of the transforming growth factor-β1/TGF-β1-activated kinase pathway.
abstract: Autonomic imbalance characterized by sympathetic predominance coinciding with diminished vagal activity is an independent risk factor in cardiovascular diseases. Several studies show that vagus nerve stimulation exerted beneficial effects on cardiac function and survival. In this study, we investigated the vagomimetic effect of pyridostigmine on left ventricular (LV) remodeling in rats after myocardial infarction. After myocardial infarction, surviving rats were treated with or without pyridostigmine (31 mg·kg⁻¹·d⁻¹) for 2 weeks, and hemodynamic parameters were measured. LV tissue was used to assess infarct size and interstitial fibrosis by Masson's trichrome and 0.1% picrosirius red staining. Protein expression of heart tissues was used to assess the efficacy of the treatment. Pyridostigmine markedly reduced myocardial infarct size and improved cardiac diastolic function. These improvements were accompanied with a significant decrease in matrix metalloproteinase-2 expression and collagen deposition. Additionally, pyridostigmine inhibited both transforming growth factor-β1 (TGF-β1) and TGF-β1-activated kinase expression in hearts postmyocardial infarction. Thus, pyridostigmine reduces collagen deposition, attenuates cardiac fibrosis, and improves LV diastolic function after myocardial infarction via TGF-β1/TGF-β1-activated kinase pathway inhibition.
authors.affiliation: Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Bi
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Kong
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Qin
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011729:Pyridostigmine Bromide / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*; D020257:Ventricular Remodeling / Q000187:drug effects*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D002800:Cholinesterase Inhibitors; D006909:Hydroxyproline; D020930:MAP Kinase Kinase Kinases; D020778:Matrix Metalloproteinase 2; D011729:Pyridostigmine Bromide; D053773:Transforming Growth Factor beta1; D000099151:MAP Kinase Kinase Kinase 7