Apoptosis

, Volume 17, Issue 1, pp 25–36

Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo

  • Lu Zhang
  • GuangZhou Zhou
  • Wei Song
  • XiaoRong Tan
  • YuQi Guo
  • Bo Zhou
  • Hongjuan Jing
  • SuJuan Zhao
  • LiangKe Chen
Original Paper

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.

Keywords

Apoptosis Atherosclerosis Lectin-like oxLDL receptor-1 Oxidized low density lipoprotein Pterostilbene Vascular endothelial cell 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Lu Zhang
    • 1
  • GuangZhou Zhou
    • 1
  • Wei Song
    • 1
  • XiaoRong Tan
    • 1
  • YuQi Guo
    • 2
  • Bo Zhou
    • 3
  • Hongjuan Jing
    • 1
  • SuJuan Zhao
    • 1
  • LiangKe Chen
    • 1
  1. 1.College of BioengineeringHenan University of TechnologyZhengzhouChina
  2. 2.Department of Obstetrics and GynecologyThe Third Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  3. 3.State Key Laboratory of Applied Organic ChemistryLanzhou UniversityLanzhouChina

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