DIFFERENCES IN EXPRESSION OF SARCOPLASMIC-RETICULUM CA2-ATPASE AND NA+-CA2+ EXCHANGER GENES BETWEEN ADJACENT AND REMOTE NONINFARCTED MYOCARDIUM AFTER MYOCARDIAL-INFARCTION()

Although cardiac failure can develop over time after myocardial infarc tion, the mechanism responsible for this is still unknown. The change of intracellular Ca2+ transport protein, such as sarcoplasmic reticulu m (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), or cardia c phenotypic modulation of contractile protein in noninfarcted myocard ium may have a important role. However, the time course in gene expres sion of sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ ex changer (Na+-Ca2+), and contractile protein in the adjacent and remote noninfarcted myocardium after myocardial infarction has not been exam ined. At 1, 3 weeks and 3 months after myocardial infarction, hemodyna mics were measured and mRNA of the left ventricle was analyzed. Left v entricular end-diastolic volume and weight increased both with time. A scites became apparent at 3 months after infarction. SR-Ca2+ mRNA leve ls in the adjacent noninfarcted myocardium were 0.7-(P<0.01), 0.9-(N.S .), and 0.7-fold (P<0.01) of control, and Na+-Ca2+ mRNA levels were 2. 1-(P<0.01), 1.4-(P<0.01), and 0.8-fold (P<0.01) of control, at 1, 3 we eks and 3 months after infarction, respectively. beta-Myosin heavy cha in (MHC) mRNA was increased to 2.1-(P<0.01), 1.5-(P<0.01), and 1.4-fol d (P<0.01), and alpha-skeletal actin was increased to 2.4-(P<0.01), 3. 8-(P<0.01), and 1.6-fold (P<0.01) control levels, at 1 week, 3 weeks a nd 3 months, respectively. In contrast, alpha-MHC mRNA level was decre ased at 1 week and 3 months after infarction. alpha-cardiac actin mRNA level did not change over time after infarction. In the remote non-in farcted myocardium, beta-MHC, alpha-skeletal actin, and Na+-Ca2+ mRNA levels were increased, but SR-Ca2+, alpha-MHC, and alpha-cardiac actin mRNA did not change after infarction. These findings suggest that: (1 ) intracellular Ca2+ handling system after myocardial infarction may b e different between adjacent and remote non-infarcted myocardium; and that (2) both decreased gene expression of SR Ca2+-ATPase and Na+-Ca2 exchanger in the adjacent non-infarcted myocardium may progress cardi ac dysfunction. (C) 1997 Academic Press Limited