Abstract
Altered calcium homeostasis may play a key role in the pathophysiology
of human heart failure. Levels of sarcoplasmic reticulum (SR) proteins
and sarcolemmal Na$^+$-Ca$^2+$ exchanger were analyzed by
Western blot in failing and nonfailing human myocardium and related
to myocardial function. Levels of the SR calcium release channel
and of calcium storage proteins (calsequestrin and calreticulin)
were not different in nonfailing and failing hearts. However, proteins
involved in calcium removal were significantly altered in the failing
human heart: (1) SR-Ca$^2+$-ATPase levels and the ratio of SR-Ca$^2+$-ATPase
to its inhibitory protein phospholamban were significantly decreased,
and (2) Na$^+$-Ca$^2+$ exchanger levels and the ratio of
Na$^+$-Ca$^2+$ exchanger to SR-Ca$^2+$-ATPase were significantly
increased. SR-Ca$^2+$-ATPase levels were closely correlated to
systolic function as evaluated by frequency potentiation of contractile
force. The frequency-dependent rise of diastolic force was inversely
correlated with protein levels of Na$^+$-Ca$^2+$ exchanger.
These findings indicate that altered expression of SR-Ca$^2+$-ATPase
and Na$^+$-Ca$^2+$ exchanger is relevant for altered systolic
and diastolic function in human heart failure.
- ,
- 10603950
- animals,
- atpase,
- calcium
- calcium,
- calcium-binding
- calreticulin,
- calsequestrin,
- cardiomyopathy,
- channel,
- congestive,
- contraction,
- dilated,
- exchanger,
- failure,
- heart
- humans,
- myocardial
- proteins,
- receptor
- release
- reticulum,
- ribonucleoproteins,
- ryanodine
- sarcoplasmic
- sodium-calcium
- {c}a$^{2+}$-transporting
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