Inflammation participates centrally in all stages of
atherosclerosis (AS), which begins with inflammatory changes in the endothelium, characterized by expression of the adhesion molecules.
Resveratrol (RSV) is a naturally occurring phytoalexin that can attenuate endothelial
inflammation; however, the exact mechanisms have not been thoroughly elucidated. Autophagy refers to the normal process of cell degradation of
proteins and organelles, and is protective against certain inflammatory
injuries. Thus, we intended to determine the role of autophagy in the antiinflammatory effects of RSV in human umbilical vein endothelial cells (HUVECs). We found that RSV pretreatment reduced
tumor necrosis factor ? (TNF/TNF?)-induced
inflammation and increased MAP1LC3B2 (
microtubule-associated protein 1 light chain 3 ? 2) expression and SQSTM1/p62 (sequestosome 1) degradation in a concentration-dependent manner. A
bafilomycin A 1 (BafA1) challenge resulted in further accumulation of MAP1LC3B2 in HUVECs. Furthermore, autophagy inhibitors
3-methyladenine (3-MA),
chloroquine as well as ATG5 and BECN1
siRNA significantly attenuated RSV-induced autophagy, which, subsequently, suppressed the downregulation of RSV-induced inflammatory factors expression. RSV also increased cAMP (cyclic
adenosine monophosphate) content, the expression of PRKA (
protein kinase A) and
SIRT1 (
sirtuin 1), as well as the activity of AMPK (
AMP-activated protein kinase). RSV-induced autophagy in HUVECs was abolished in the presence of inhibitors of ADCY (
adenylyl cyclase, KH7), PRKA (H-89), AMPK (compound C), or
SIRT1 (
nicotinamide and
EX-527), as well as ADCY, PRKA, AMPK, and
SIRT1 siRNA transfection, indicating that the effects of RSV on autophagy induction were dependent on cAMP, PRKA, AMPK and
SIRT1. In conclusion, RSV attenuates endothelial
inflammation by inducing autophagy, and the autophagy in part was mediated through the activation of the cAMP-PRKA-AMPK-SIRT1 signaling pathway.