Furthermore, we consistently observed inhibition of ATM-DDR signaling during pressure overload in both CAG-Caren Tg and Hint1+/− mice, suggesting that Caren blocks Hint1 upregulation brought on by pathological stress and protects against HF development through (1) maintaining mitochondrial respiratory capacity and (2) suppressing ATM-DDR signaling. This evidence concerns the gene HINT1 and hydrops fetalis.