title: Labedipinedilol-A prevents lysophosphatidylcholine-induced vascular smooth muscle cell death through reducing reactive oxygen species production and anti-apoptosis.
abstract: OBJECTIVE
  Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis.
  
  
  RESULTS
  VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis. Labedipinedilol-A attenuated lysoPC-induced cell death and Ca(2+) influx. It also reduced reactive oxygen species (ROS) production evoked by lysoPC and down-regulated expressions of NAD(P)H oxidase subunits, Nox1 and Rac1. Moreover, it inhibited lysoPC-induced phosphorylation of MAPK including ERK1/2, JNK, and p38. It mitigated the dissipation of mitochondrial transmembrane potential induced by lysoPC. Lastly, labedipinedilol-A inhibited lysoPC-induced apoptosis with attenuation of caspase-3/-9 activations and modulation of Bax/Bcl-2 protein expressions.
  
  
  CONCLUSIONS
  Labedipinedilol-A can suppress lysoPC-induced VSMCs death via reducing ROS production and anti-apoptosis. These protective effects are potentially mediated through the inhibition of Ca(2+) influx, down-regulation of the NAD(P)H oxidase subunits (Nox1/Rac1) and MAPK signaling, and attenuation of mitochondrial depolarization. Thus, labedipinedilol-A may have a valuable role in the preventing atherosclerosis associated with hyperlipidemia.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Jong-Hau
authors: JH
authors: Hsu
authors: Jiunn-Ren
authors: JR
authors: Wu
authors: Shu-Fen
authors: SF
authors: Liou
authors: Huai-Min
authors: HM
authors: Chen
authors: Zen-Kong
authors: ZK
authors: Dai
authors: Ing-Jun
authors: IJ
authors: Chen
authors: Jwu-Lai
authors: JL
authors: Yeh