CACNB4 attenuates cardiac dysfunction by regulating calcium and ATP levels via interaction with RyR2

CACNB4 is suspected to be involved in cardiac contraction, its specific role and the underlying mechanisms are not elucidated. We analyzed gene expression profiles of peripheral blood mononuclear cells (PBMCs) from heart failure patients using the GSE235757 data set from the NCBI GEO database. KEGG enrichment analysis was performed to identify pathways associated with differentially expressed genes. Analysis of the GSE235757 data set revealed a significant downregulation of CACNB4 expression in PBMCs of heart failure patients, particularly in the "Cardiac muscle contraction" pathway. Western blot analysis confirmed a reduction in CACNB4 expression in hypoxic myocardial cells and heart tissue from heart failure mice. Overexpression of CACNB4 improved cardiac function, reduced infarct size, alleviated myocardial damage, via enhancing ATP and CA²⁺ levels. Further analysis identified an interaction between CACNB4 and RyR2, which improve CA²⁺ and ATP levels. This study demonstrated that CACNB4 interacts with RyR2 to regulate intracellular CA²⁺ and ATP levels, which are critical for maintaining cardiac function.