This PDF file includes:

• Table S1. Clinical characteristics of HF cohort cases.
• Table S2. Multivariable logistic regression analysis of β5i and chymotrypsin-like activity associated with HF (n = 38).
• Fig. S1. Analysis of the β5i protein levels in rat neonatal cardiomyocytes.
• Fig. S2. KO of β5i inhibits phenylephrine (PE)–induced cardiomyocyte hypertrophy.
• Fig. S3. Analysis of autophagic influx in rat neonatal cardiomyocytes.
• Fig. S4. KO of β5i decreases chymotrypsin-like activity in mice after TAC operation.
• Fig. S5. Analysis of the β5i expression and survival rate in WT and β5i-Tg mice.
• Fig. S6. Knockdown of ATG5 by rAAV9-siATG5 in mice abolishes the cardioprotective effect of β5i KO after pressure overload.
• Fig. S7. The summarized diagram showing that the proposed mechanisms underlying β5i regulate cardiac hypertrophy.

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