title: Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo.
abstract: Vascular endothelial cell (VEC) apoptosis is the main event occurring during the development of atherosclerosis. Pterostilbene (PT), a natural dimethylated analog of resveratrol, has been the subject of intense research in cancer and inflammation. However, the protective effects of PT against oxidized low-density lipoprotein (oxLDL)-induced apoptosis in VECs have not been clarified. We investigated the anti-apoptotic effects of PT in vitro and in vivo in mice. PT at 0.1-5 μM possessed antioxidant properties comparable to that of trolox in a cell-free system. Exposure of human umbilical vein VECs (HUVECs) to oxLDL (200 μg/ml) induced cell shrinkage, chromatin condensation, nuclear fragmentation, and cell apoptosis, but PT protected against such injuries. In addition, PT injection strongly decreased the number of TUNEL-positive cells in the endothelium of atherosclerotic plaque from apoE(-/-) mice. OxLDL increased reactive oxygen species (ROS) levels, NF-κB activation, p53 accumulation, apoptotic protein levels and caspases-9 and -3 activities and decreased mitochondrial membrane potential (MMP) and cytochrome c release in HUVECs. These alterations were attenuated by pretreatment with PT. PT inhibited the expression of lectin-like oxLDL receptor-1 (LOX-1) expression in vitro and in vivo. Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease. PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis.
authors.affiliation: College of Bioengineering, Henan University of Technology, Zhengzhou, China. chaperones@163.com
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Guangzhou
authors.initials: G
authors.lastname: Zhou
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Tan
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Jing
authors.forename: Sujuan
authors.initials: S
authors.lastname: Zhao
authors.forename: Liangke
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D020011:Protective Agents; D013267:Stilbenes; C099252:oxidized low density lipoprotein; C107773:pterostilbene