Skip to main content
padlock icon - secure page this page is secure

Poly(ADP‐ribose) polymerase 1 deficiency increases nitric oxide production and attenuates aortic atherogenesis through downregulation of arginase II

Buy Article:

$52.00 + tax (Refund Policy)

Poly (ADP‐ribose) polymerase (PARP) plays an important role in endothelial dysfunction, leading to atherogenesis and vascular‐related diseases. However, whether PARP regulates nitric oxide (NO), a key regulator of endothelial function, is unclear so far. We investigated whether inhibition of PARP‐1, the most abundant PARP isoform, prevents atherogenesis by regulating NO production and tried to elucidate the possible mechanisms involved in this phenomenon. In apolipoprotein E‐deficient (apoE−/−) mice fed a high‐cholesterol diet for 12 weeks, PARP‐1 inhibition via treatment with 3,4‐dihydro‐54‐(1‐piperindinyl) butoxy‐1(2H)‐isoquinoline (DPQ) or PARP‐1 gene knockout reduced aortic atherosclerotic plaque areas (49% and 46%, respectively). Both the groups showed restored NO production in mouse aortas with reduced arginase II (Arg II) expression compared to that in the controls. In mouse peritoneal macrophages and aortic endothelial cells (MAECs), PARP‐1 knockout resulted in lowered Arg II expression. Moreover, phosphorylation of endothelial NO synthase (eNOS) was preserved in the aortas and MAECs when PARP‐1 was inhibited. Reduced NO production in vitro due to PARP‐1 deficiency could be restored by treating the MAECs with oxidized low‐density lipoprotein treatment, but this effect could not be achieved with peritoneal macrophages, which was likely due to a reduction in the expression of induced NOS expression. Our findings indicate that PARP‐1 inhibition may attenuate atherogenesis by restoring NO production in endothelial cells and thus by reducing Arg II expression and consequently arginase the activity.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: arginase II; atherogenesis; nitric oxide; poly (ADP‐ribose) polymerase 1

Document Type: Research Article

Publication date: January 1, 2017

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more