title: Influence of atorvastatin on angiotensin I metabolism in resting and TNF-α -activated rat vascular smooth muscle cells.
abstract: BACKGROUND
  Vascular smooth muscle cells (VSMCs) are essential for maintaining vasculature homeostasis and function. By influence on its growth and activation both proinflammatory cytokines and peptides of the renin-angiotensin system (RAS) are potent regulators of VSMCs. Interestingly, angiotensin (Ang) II and Ang-(1-7) elicit opposite effects on VSMC activation, differentiation and proliferation. It has been suggested that statins, besides anti-inflammatory effects, may also modulate VSMC activation by their influence on the RAS.
  
  
  METHODS
  The effect of atorvastatin on Ang I metabolism in a culture of explanted rat VSMCs was examined by liquid chromatography-mass spectrometry (LC-MS); expression of mRNA of the main RAS enzymes in VSMC was assessed by real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  In VSMC culture Ang-(1-7) was identified as a major product of Ang I metabolism. In this setting, TNF-α (1 ng/ml) caused a decrease in the conversion of Ang I to Ang-(1-7). This effect was accompanied by a decrease of mRNA expression of neutral endopeptidase (NEP) and angiotensin converting enzyme 2 (ACE2) and increase of mRNA of ACE. Interestingly, atorvastatin (3 μM) attenuated the effects of TNF-α on Ang-(1-7) production as well as reversed the influence of TNF-α on ACE and ACE2 expression.
  
  
  CONCLUSIONS
  Enhancement by atorvastatin of the ACE2/Ang-(1-7) axis in VSMCs could represent a new and beneficial mechanism on cardiovascular action of this widely used drug.
authors: School of Medicine, Jagiellonian University, Poland.
authors: Maciej
authors: M
authors: Suski
authors: School of Medicine, Jagiellonian University, Poland.
authors: Anna
authors: A
authors: Gębska
authors: School of Medicine, Jagiellonian University, Poland mfolszan@cyf-kr.edu.pl.
authors: Rafal
authors: R
authors: Olszanecki
authors: School of Medicine, Jagiellonian University, Poland.
authors: Aneta
authors: A
authors: Stachowicz
authors: School of Medicine, Jagiellonian University, Poland.
authors: Danuta
authors: D
authors: Uracz
authors: School of Medicine, Jagiellonian University, Poland.
authors: Jozef
authors: J
authors: Madej
authors: School of Medicine, Jagiellonian University, Poland.
authors: Ryszard
authors: R
authors: Korbut
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D017208:Rats, Wistar; D012146:Rest; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D006538:Heptanoic Acids; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000803:Angiotensin I; D000069059:Atorvastatin; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D015260:Neprilysin
keywords: Angiotensin; angiotensin converting enzyme; renin; statin; vascular smooth muscle cells