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 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 alpha- and beta-sarcoglycan and beta-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 Ca(2+)-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 alpha-sarcoglycan, beta-sarcoglycan, and beta-dystroglycan may be involved in the development of right ventricular failure in MCT rats.
Daicho
Takuya
T
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji 192-0392, Japan.
Daisho
Yoriko
Y
Kojima
Suguru
S
Takano
Saori
S
Tejima
Yugo
Y
Marunouchi
Tetsuro
T
Takagi
Norio
N
Takeo
Satoshi
S
Tanonaka
Kouichi
K
D000818:Animals; D002154:Calpain / Q000378:metabolism; D049030:Dystroglycans / Q000378:metabolism; D049028:Dystrophin-Associated Protein Complex / Q000378:metabolism*; D006333:Heart Failure / Q000201:enzymology / Q000378:metabolism*; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016686:Monocrotaline; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D049031:Sarcoglycans / Q000378:metabolism; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000201:enzymology / Q000378:metabolism*
D049028:Dystrophin-Associated Protein Complex; D049031:Sarcoglycans; D049030:Dystroglycans; D016686:Monocrotaline; D002154:Calpain; C449000:m-calpain; D020778:Matrix Metalloproteinase 2