Decrease in sarcoglycans and dystrophin in failing heart following acute myocardial infarction.
OBJECTIVE
Genetic defects in several sarcoglycans (SGs) and dystrophin (Dys) play a critical role in cardiomyopathy. The present study was designed to determine whether changes in SGs and Dys might occur in animals with chronic heart failure (CHF) induced by acute myocardial infarction (AMI), which have no genetic defects.


METHODS
AMI was induced by the left coronary artery ligation (CAL) in rats. The hemodynamic parameters of the 2- and 8-week CAL (2w- and 8w-CAL) rats were measured and the myocardial SGs, Dys, calpain, and calpastatin levels were determined by the Western blot method. Myocardial calpain-like protease activity was evaluated as caseinolysis activity.


RESULTS
Increases in left ventricular end-diastolic pressure (LVEDP) and right ventricular systolic pressure, and a decrease in +/-dP/dt were observed at the 2nd week, whereas cardiac output index (COI) was preserved. In contrast, the 8w-CAL rats showed a further increment in LVEDP with low COI. alpha-SG of the viable left ventricle (LV), and septum (Sep) of the 8w-CAL rat decreased (60-70% of the control). The alpha- and beta-SGs of the right ventricle (RV) of the 2w- and 8w-CAL rats were reduced, while gamma- and delta-SGs in the three regions did not change significantly. Dys in the viable LV and RV of the 8w-CAL rat decreased (75% of the control). The amount of m-calpain in the three regions of the 2w- and 8w-CAL rats increased (140-200% of the control), whereas the endogenous calpain inhibitor, calpastatin, did not change significantly. The in vitro degradation studies using purified m-calpain or cytosolic fractions of the 8w-CAL rat heart suggested a reduction in SGs and Dys by calpain.


CONCLUSIONS
The results suggest that a decrease in SGs and Dys may play an important role in the pathophysiology of CHF following AMI.
Yoshida
Hiroyuki
H
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Takahashi
Masaya
M
Koshimizu
Miki
M
Tanonaka
Kouichi
K
Oikawa
Ryo
R
Toyo-oka
Teruhiko
T
Takeo
Satoshi
S
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western / Q000379:methods; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000378:metabolism; D002154:Calpain / Q000032:analysis / Q000378:metabolism; D002303:Cardiac Output, Low / Q000378:metabolism*; D046508:Culture Techniques; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis / Q000378:metabolism*; D006339:Heart Rate; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism*; D023421:Models, Animal; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D049031:Sarcoglycans; D012508:Sarcolemma / Q000378:metabolism
D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans; C033668:calpastatin; D002154:Calpain