title: Atorvastatin may delay cardiac aging by upregulating peroxisome proliferator-activated receptors in rats.
abstract: OBJECTIVE
  To investigate the effect of atorvastatin on cardiac aging in rats.
  
  
  METHODS
  Ninety 20-month-old Wistar rats were administered oral atorvastatin (AVT; 10 or 1 mg·kg(-1)·day(-1)) or saline for 4 months. At the end of the experiment, age-related changes in hearts were measured.
  
  
  RESULTS
  Compared with young rats, obvious increases were found in the aging rats in left ventricle thickness, diameter of cardiocytes, collagen deposition, the ratio of type I/type III collagen, β-galactosidase and malondialdehyde (MDA), and obvious decreases were found in superoxide dismutase (SOD), catalase (CAT) and nitric oxide synthase (NOS). The treatment with AVT led to significant decreases in the thickness of the left ventricle, diameter of cardiocytes, collagen deposition, I/III collagen ratio, MDA, β-galactosidase and increases in the activity of SOD, CAT and NOS. Some aging-related inflammatory cytokines like interleukin (IL)-1β, tumour necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-9 were found to be overexpressed in the aging rats. AVT treatment could inhibit the expression of IL-1β, TNF-α and MMP-9 on both the mRNA and protein levels, and increase the expression of peroxisome proliferator-activated receptors (PPAR-α/β/δ/γ). Pretreatment with PPAR inhibitors attenuated the inhibitory effect of AVT on the expression of inflammatory cytokines.
  
  
  CONCLUSIONS
  AVT may retard the cardiac aging process by upregulating PPARs.
authors.affiliation: Aviation and Nautical Medical Center, Navy General Hospital, Beijing, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Minggao
authors.initials: M
authors.lastname: Li
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Liu
authors.forename: Chunguang
authors.initials: C
authors.lastname: Han
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010088:Oxidoreductases / Q000096:biosynthesis; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D047492:Peroxisome Proliferator-Activated Receptors; D011758:Pyrroles; D000069059:Atorvastatin; D010088:Oxidoreductases