Simvastatin impairs the induction of pulmonary fibrosis caused
by a western style diet: a preliminary study

J 2015

Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study

KRUŽLIAK, Peter; David L. HARE; Václav ZVONÍČEK; Jan KLIMAS; Anthony ZULLI et al.

Základní údaje

Originální název

Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study

Autoři

KRUŽLIAK, Peter; David L. HARE; Václav ZVONÍČEK; Jan KLIMAS a Anthony ZULLI

Vydání

Journal of Cellular and Molecular Medicine, Hoboken, Wiley-Blackwell, 2015, 1582-4934

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/15:00085440

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

simvastatin; fibrosis; Hsp70; Hsp90; diet; cholesterol; methionine

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 12. 2015 13:54, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

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 5mg/kg/day simvastatin orally (MCS). After 4weeks, 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.

Citovat

KRUŽLIAK, Peter; David L. HARE; Václav ZVONÍČEK; Jan KLIMAS a Anthony ZULLI. Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study. Journal of Cellular and Molecular Medicine. Hoboken: Wiley-Blackwell, 2015, roč. 19, č. 11, s. 2647-2654. ISSN 1582-4934. Dostupné z: https://doi.org/10.1111/jcmm.12637.

@article{1322314,
   author = {Kružliak, Peter and Hare, David L. and Zvoníček, Václav and Klimas, Jan and Zulli, Anthony},
   article_location = {Hoboken},
   article_number = {11},
   doi = {https://doi.org/10.1111/jcmm.12637},
   keywords = {simvastatin; fibrosis; Hsp70; Hsp90; diet; cholesterol; methionine},
   language = {eng},
   issn = {1582-4934},
   journal = {Journal of Cellular and Molecular Medicine},
   title = {Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study},
   volume = {19},
   year = {2015}
}

TY  - JOUR
ID  - 1322314
AU  - Kružliak, Peter - Hare, David L. - Zvoníček, Václav - Klimas, Jan - Zulli, Anthony
PY  - 2015
TI  - Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study
JF  - Journal of Cellular and Molecular Medicine
VL  - 19
IS  - 11
SP  - 2647-2654
EP  - 2647-2654
PB  - Wiley-Blackwell
SN  - 15824934
KW  - simvastatin
KW  - fibrosis
KW  - Hsp70
KW  - Hsp90
KW  - diet
KW  - cholesterol
KW  - methionine
N2  - 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 5mg/kg/day simvastatin orally (MCS). After 4weeks, 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.
ER  -

KRUŽLIAK, Peter; David L. HARE; Václav ZVONÍČEK; Jan KLIMAS a Anthony ZULLI. Simvastatin impairs the induction of pulmonary fibrosis caused by a western style diet: a preliminary study. \textit{Journal of Cellular and Molecular Medicine}. Hoboken: Wiley-Blackwell, 2015, roč.~19, č.~11, s.~2647-2654. ISSN~1582-4934. Dostupné z: https://doi.org/10.1111/jcmm.12637.

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