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Title: Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study.
Austin Authors: Kruzliak, Peter;Hare, David L ;Zvonicek, Vaclav;Klimas, Jan;Zulli, Anthony
Affiliation: Centre for Chronic Disease Prevention & Management (CCDPM), Western CHRE, College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia
Department of Anesthesiology and Intensive Care Medicine, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia
International Clinical Research Center, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic
Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Nov-2015
Date: 2015-08-25
Publication information: Journal of cellular and molecular medicine 2015; 19(11): 2647-54
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.
DOI: 10.1111/jcmm.12637
ORCID: 0000-0001-9554-6556
Journal: Journal of cellular and molecular medicine
PubMed URL: 26304628
Type: Journal Article
Subjects: Hsp70
Appears in Collections:Journal articles

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