Nevertheless, cardiac hypertrophy was remained in TAC mice treated by HMGB1 box A at the same time, accompanied by the trend of preservation of LV systolic function, indicating that HMGB1 may be of crucial importance in TAC‐induced cardiac injury, and heart failure induced by pressure overload may be postponed by local HMGB1 blocking. Here, HMGB1 is linked to heart failure.