title: Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study.
abstract: The role of an atherogenic diet in causing pulmonary fibrosis has received little attention and simvastatin has been shown to reduce pulmonary fibrosis in animal models. To determine if an atherogenic diet can induce pulmonary fibrosis and whether simvastatin treatment is beneficial by up-regulating heat shock protein 70 and 90. New Zealand white rabbits (n = 15) were divided: Group 1 (control); Group 2 (MC) received a normal rabbit diet with 1% methionine plus 0.5% cholesterol (atherogenic diet). Group 3 received the same diet as the MC group plus 5 mg/kg/day simvastatin orally (MCS). After 4 weeks, the lungs were collected and analysed. Picrosirus red staining of lung interstitial collagen content showed that the atherogenic diet increased fibrosis 2.9-fold (P < 0.05), bronchiole adventitial collagen was increased 2.3-fold (P < 0.05) and bronchiole epithelium was increased 34-fold (P < 0.05), and simvastatin treatment severely reduced this effect (P < 0.05). Western blot analysis showed that the atherogenic diet significantly reduced lung Hsp70 protein by 22% (P < 0.05) and Hsp90 protein by 18% (P < 0.05) and simvastatin treatment did not affect this result. However, aortic hyper-responsiveness to vasoconstrictors (angiotensin II and phenylephrine) were markedly reduced by simvastatin treatment. We report that an atherogenic diet stimulates pulmonary fibrosis and reduces lung Hsp70/Hsp90 protein concentration. Simvastatin impairs this by mechanisms unrelated to Hsp70/Hsp90, but possibly a reduction in angiotensin II receptor or alpha adrenergic receptor pathways. These results could have implications in idiopathic pulmonary fibrosis.
authors: International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors: Peter
authors: P
authors: Kruzliak
authors: Departments of Cardiology and Medicine, University of Melbourne, Austin Health, Melbourne, VIC, Australia.
authors: David L
authors: DL
authors: Hare
authors: International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.|Department of Anesthesiology and Intensive Care Medicine, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors: Vaclav
authors: V
authors: Zvonicek
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors: Jan
authors: J
authors: Klimas
authors: Department of Anesthesiology and Intensive Care Medicine, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.|Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, College of Health and Biomedicine, Victoria University, St Albans, VIC, Australia.
authors: Anthony
authors: A
authors: Zulli
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D004036:Diet, Atherogenic / Q000009:adverse effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D011945:Receptors, Angiotensin; D019821:Simvastatin
keywords: Hsp70; Hsp90; cholesterol; diet; fibrosis; methionine; simvastatin