Key result
Co-overexpression of CSQ and TRN in mice normalized SR Ca2+ release compared with CSQ overexpression alone, but resulted in reduced survival, increased cardiac fibrosis, and depressed contractility.
Population
Transgenic mice models (TG with heart-specific overexpression of calsequestrin, TG with co-overexpression of…
Comparison
Co-overexpression of calsequestrin and triadin… vs Overexpression of calsequestrin alone (TG) and…
Design
Preclinical
Authors
Loading...
May caution against co-modulating SR proteins despite normalized Ca2+ release; leaves open triadin-calsequestrin ratio as therapeutic target in human cardiomyopathy.
The triadin-to-calsequestrin ratio is a critical modulator of SR Ca2+ signaling, where co-overexpression normalizes Ca2+ release but paradoxically worsens survival and contractile function due to fibrosis and blunted beta-adrenergic response.
Kučerová et al. (2012) studied Impaired intracellular Ca2+ signaling and contractile function. Co-overexpression of CSQ and TRN (TG(CxT)) vs. Overexpression of CSQ alone (TG(CSQ)) and wild-type hearts was evaluated on Intracellular Ca2+ concentration peak amplitude, survival rate, cardiac fibrosis, and basal contractility. Co-overexpression of CSQ and TRN in mice normalized SR Ca2+ release compared with CSQ overexpression alone, but resulted in reduced survival, increased cardiac fibrosis, and depressed contractility.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: