Regional alterations in SR Ca(2+)-ATPase, phospholamban, and HSP-70 expression in chronic hibernating myocardium.
We sought to identify mechanisms for chronic dysfunction in hibernating myocardium. Pigs were instrumented with a left anterior descending artery stenosis for 3 mo. Angiography demonstrated high-grade stenoses and hibernating myocardium with 1) severe anterior hypokinesis (P < 0.001 vs. shams), 2) reduced subendocardial perfusion [0.73 +/- 0.05 (SE) vs. 1.01 +/- 0.06 ml. min(-1). g(-1) in normal, P < 0.001], and 3) critically reduced adenosine flow (1.0 +/- 0.17 vs. 3.84 +/- 0.26 ml. min(-1). g(-1) in normal, P < 0.001). Histology did not reveal necrosis. Northern blot analysis of hibernating myocardium demonstrated regional downregulation in mRNAs for sarcoplasmic reticulum (SR) proteins phospholamban (0.76 +/- 0.08 vs. 1.07 +/- 0.06, P < 0.02) and SR Ca(2+)-ATPase (0.83 +/- 0.06 vs. 1.02 +/- 0.06, P < 0.05) with no change in calsequestrin (1.08 +/- 0.06 vs. 0.96 +/- 0.05, P = not significant). Heat shock protein (HSP)-70 mRNA was regionally induced in hibernating myocardium (2.4 +/- 0.3 vs. 1.0 +/- 0.11, P < 0.01). Directionally similar changes were confirmed by Western blot analysis of respective proteins. Our results indicate that hibernating myocardium exhibits a molecular phenotype that on a regional basis is similar to end-stage ischemic cardiomyopathy. This supports the hypothesis that SR dysfunction from reversible ischemia may be an early defect in the progression of left ventricular dysfunction.
Fallavollita
J A
JA
Department of Veterans Affairs, Western New York Health Care System, Buffalo, New York 14214, USA.
Jacob
S
S
Young
R F
RF
Canty
J M
JM
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006439:Hemodynamics; D017682:Myocardial Stunning; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution; D000099211:Phospholamban
D000241:Adenosine; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D000099211:Phospholamban