Our results highlight the interaction of Yulink with PPARγ in regulating Serca2 expression and suggest a mechanistic role of the Yulink in the development of human heart failure and SCD.-Tsai, C.-T., Kuo, M.-W., Lin, J.-L., Yu, A. L., Yu, J.
Our findings show a crucial role of LRP1/Pyk2/HIF-1α in hypoxia-induced cardiomyocyte SERCA2 downregulation, a pathophysiological process closely associated with heart failure.
These data reveal myofibrillar Ca(2+)-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.
In this review we describe the drugs adopted in clinical practice that activate SERCA2a/b function as well as new promising therapeutic tools using SERCA2 viral gene delivery to improve cardiac function and treat heart failure.
A reduced activity and expression of SERCA2 protein have been described in heart failure and diabetic cardiomyopathy, resulting in an altered Ca(2+) handling and cardiac contractility.
The observation that ATP2A2rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF.
Therapeutic upregulation of SERCA2 expression using replication deficient adenoviral expression vectors, pharmacological interventions using thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel metabolically active compounds are currently under investigation for the treatment of uncompensated cardiac hypertrophy and heart failure.
During end-stage human heart failure, we have demonstrated that type 1 IP3R (IP3R1) mRNA and protein levels are up-regulated, in contrast to other cardiac calcium regulatory proteins, such as the type 2 ryanodine receptor (RYR2) and type IIa sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), which are down-regulated.