12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival

G. Weisinger*, M. Grafi-Cohen, M. Hirsh, E. Knoll, O. Sharon, A. Many, R. Limor, N. Stern

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Considerable evidence has been published demonstrating the importance of lipoxygenase enzymes for vascular smooth muscle cell (VSMC) growth. The current study sets out to determine whether or not 12-lipoxygenase (12LO) is also important for human placental VSMC survival. Both a pharmacological and two 12LO antisense knockdown approaches were applied. The 12LO inhibitor baicalien induced a 2-2.5-fold increase in cell death, which appeared to result from apoptosis, as indicated by DNA fragmentation, activation of procaspase 3 to caspase 3 and cytochrome C release from the mitochondria to the cytosol. This apoptosis could be prevented by treatment with the 12LO product, 12 hydroxyeicosatetraenoic acid (12HETE). Human platelet-type 12LO-antisense knockdown, by either plasmid transfection or adeno-associated virus (AAV) infection also induced substantial VSMC death over controls, which could also be prevented by treatment with 12HETE, but not 5HETE. Hence, biochemical 12LO inhibition or 12LO-antisense knockdown in VSMC can induce programmed cell death. These observations suggest a previously unrecognized association between human VSMC survivability and 12LO.

Original languageEnglish
Pages (from-to)1586-1593
Number of pages8
JournalExperimental Cell Research
Issue number10
StatePublished - 10 Jun 2013


  • Apoptosis
  • Baicalein
  • Human
  • Lipoxygenase
  • Smooth-muscle


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