Alterations in Dystrophin-Related Glycoproteins in Development of Right Ventricular Failure in Rats

Genetic depletion of the dystrophin-related glycoprotein (DRGP) complex causes cardiomyopathy in animals and humans. The present study was undertaken to explore the possible involvement of alterations in DRGP in the development of the right ventricular failure in monocrotaline-administered rats (MCT...

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Bibliographic Details
Published in:	Journal of Pharmacological Sciences Vol. 111; no. 4; pp. 405 - 415
Main Authors:	Daicho, Takuya, Daisho, Yoriko, Kojima, Suguru, Takano, Saori, Tejima, Yugo, Marunouchi, Tetsuro, Takagi, Norio, Takeo, Satoshi, Tanonaka, Kouichi
Format:	Journal Article
Language:	English
Published:	Japan Elsevier B.V 2009 The Japanese Pharmacological Society Elsevier
Subjects:	Animals calpain Calpain - metabolism Dystroglycans - metabolism Dystrophin-Associated Protein Complex - metabolism dystrophin-related glycoprotein Heart Failure - enzymology Heart Failure - metabolism Heart Ventricles - enzymology Heart Ventricles - metabolism Hemodynamics - drug effects Hypertrophy, Right Ventricular - chemically induced Male matrix metalloproteinase Matrix Metalloproteinase 2 - metabolism Monocrotaline Myocardium - enzymology Myocardium - metabolism Rats Rats, Wistar right ventricular failure Sarcoglycans - metabolism Time Factors Ventricular Dysfunction, Right - enzymology Ventricular Dysfunction, Right - metabolism calpain matrix metalloproteinase right ventricular failure dystrophin-related glycoprotein monocrotaline
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Summary:	Genetic depletion of the dystrophin-related glycoprotein (DRGP) complex causes cardiomyopathy in animals and humans. The present study was undertaken to explore the possible involvement of alterations in DRGP in the development of the right ventricular failure in monocrotaline-administered rats (MCT rats). At the 6th and 8th weeks after subcutaneous administration of 60 mg/kg monocrotaline, echocardiographic examination showed that cardiac output indices were decreased and that the right ventricular Tei indices were increased, suggesting that right ventricular failure occurs, at the latest, by 6 weeks after monocrotaline-administration. The levels of α- and β-sarcoglycan and β-dystroglycan in the right ventricle of the MCT rats at the 6th and 8th weeks were markedly decreased, and these decreases were inversely related to the increase in the right ventricular Tei index of the MCT-administered animals. The content and activity of the Ca2+-activated neutral protease m-calpain in the right ventricle of the MCT rats were increased at the 4th to 8th weeks and those of matrix metalloproteinase-2, at the 6th and 8th weeks. These results suggest that m-calpain– and/or matrix metalloproteinase-2–mediated alterations in the contents of α-sarcoglycan, β-sarcoglycan, and β-dystroglycan may be involved in the development of right ventricular failure in MCT rats.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1347-8613 1347-8648
DOI:	10.1254/jphs.09208FP