miR-155 down-regulation protects the heart from hypoxic damage by activating fructose metabolism in cardiac fibroblasts

•miR-155 suppresses splicing factor SKIV2L2 expression by targeting it’s 3′ UTR.•miR-155 deletion enhances SKIV2L2 expression and its interaction with TRA2A.•SKIV2L2/TRA2A complex suppresses alternative splicing of HIF1α pre-mRNA to form circHIF1α.•circHIF1α deletion contributes to fructose metabolism by increasing the production of KHK-C.•Exogenous delivery of SKIV2L2 reduces damage in the infarcted heart.•miR-155 downregulation protects the heart from hypoxic injury by activating fructose metabolism.