These results suggest that XBP1 regulates VEGF-mediated cardiac angiogenesis, which contributes to the progression of adaptive hypertrophy, and might provide novel targets for prevention and treatment of heart failure.
Markers of UPR [binding immunoglobulin protein (BiP), phosphorylated (P-) eukaryotic initiation factor (eIF2α), and X-box binding protein (XBP1)] were significantly increased in HF, whereas LVAD support significantly decreased BiP, P-eIF2α, and XBP1s levels.
These results provide the first clear link between miRNAs and direct regulation of XBP1 in heart failure and reveal that miR-214 and miR-30* synergistically regulates cardiac VEGF expression and angiogenesis by targeting XBP1 in the progression from adaptive hypertrophy to heart failure.