Thus the SIRT1-activating effects of SIL reported in the present study provides a new and exciting mechanistic explanation to utilize this drug and potentially other PDE-5 inhibitors in reducing ischemic heart tissue damages as well as pulmonary hypertension, considering the essential role played by SIRT1 in regulating cell defenses and survival in response to stress [10], [11]. Here, PDE5A is linked to pulmonary arterial hypertension.