Abstract
To determine whether reduced sarcoplasmic reticulum (SR) Ca$^2+$-adenosinetriphosphatase
(ATPase) (SERCA2) activity contributes to delayed myocardial relaxation
during chronic left ventricular hypertrophy (LVH) progression, LVH
was produced in rats by abdominal aortic coarctation. Systolic and
diastolic functions were assessed in vivo 8 and 16 wk after surgery,
and compositional alterations in LV myocardium SERCA2 concentration,
myosin heavy chain (MHC) isoenzymes, and tissue collagen were correlated
with the development of prolonged isovolumic relaxation and impaired
cardiac performance over time. Myocardial relaxation was prolonged
in 8-wk banded rats, despite normal isovolumic systolic function
and LV end-diastolic pressure (LVEDP). No significant alterations
in SERCA2 protein, beta-MHC, or fibrillar collagen levels were observed
at this early time point. In contrast, LV SERCA2, beta-MHC, and fibrillar
collagen concentrations were all significantly altered in 16-wk banded
rats. These late compositional changes were associated with reduced
cardiac performance, as manifested by a significant elevation in
LVEDP (14 +/- 2 mmHg). The 34\% decrease in SERCA2 protein was associated
with reduced SR Ca$^2+$ uptake and an even greater reduction
(76\%) in SERCA2 mRNA. SERCA2 mRNA levels were also significantly
reduced to 43 +/- 10\% of sham-operated rats 8 wk after banding,
despite unchanged SERCA2 protein levels and normal SR Ca$^2+$
uptake. These results argue against a significant contribution of
SERCA2 downregulation to the subtle alterations in myocardial relaxation
observed in compensated LVH. However, the early reduction in SERCA2
mRNA levels may serve as a molecular marker for impaired cardiac
performance during the transition from compensated LVH to heart failure.
- 9176313
- active,
- adenosine
- animals,
- atpase,
- biological
- calcium,
- calorimetry,
- cardium,
- chains,
- diastole,
- down-regulation,
- expression,
- factors,
- fluorescence,
- gene
- gov't,
- heart
- heavy
- hydroxyproline,
- hypertrophy,
- isoenzymes,
- kinetics,
- left
- male,
- messenger,
- microsomes,
- myo,
- myocardium,
- myosin
- non-u.s.
- p.h.s.,
- rats,
- research
- reticulum,
- rna,
- sarcoplasmic
- spectrometry,
- sprague-dawley,
- support,
- thermodynamics,
- time
- transport,
- triphosphate,
- u.s.
- ventricles,
- ventricular,
- {c}a$^{2+}$-transporting
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