OUP user menu

DJ-1/park7 modulates vasorelaxation and blood pressure via epigenetic modification of endothelial nitric oxide synthase

Kyung Jong Won, Seung Hyo Jung, Soo Hyun Jung, Kang Pa Lee, Hwan Myung Lee, Dong-Youb Lee, Eun-Seok Park, Junghwan Kim, Bokyung Kim
DOI: http://dx.doi.org/10.1093/cvr/cvt274 473-481 First published online: 9 December 2013

Abstract

Aims DJ-1/park7, a multifunctional protein, may play essential roles in the vascular system. However, the function of DJ-1/park7 in vascular contractility has remained unclear. The present study was designed to investigate whether the DJ-1/park7 is involved in the regulation of vascular contractility and systolic blood pressure (SBP).

Methods and results Norepinephrine (NE) elevated contraction in endothelium-intact vessels in a dose-dependent manner, to a greater extent in DJ-1/park7 knockout (DJ-1/park7−/−) mice than in wild-type (DJ-1/park7+/+) mice. Acetylcholine inhibited NE-evoked contraction in endothelium-intact vessels, and this was markedly impaired in DJ-1/park7−/− mice compared with DJ-1/park7+/+. Nitric oxide (NO) production (82.1 ± 2.8% of control) and endothelial NO synthase (eNOS) expression (61.7 ± 8.9%) were lower, but H2O2 production (126.4 ± 8.6%) was higher, in endothelial cells from DJ-1/park7−/− mice than in those from DJ-1/park7+/+ controls; these effects were reversed by DJ-1/park7-overexpressing endothelial cells from DJ-1/park7−/− mice. Histone deacetylase (HDAC)-1 recruitment and H3 histone acetylation at the eNOS promoter were elevated and diminished, respectively, in DJ-1/park7−/− mice compared with DJ-1/park7+/+ controls. Moreover, SBP was significantly elevated in DJ-1/park7−/− mice compared with DJ-1/park7+/+ controls, but this elevation was inhibited in mice treated with valproic acid, an inhibitor of Class I HDACs including HDAC-1.

Conclusion These results demonstrate that DJ-1/park7 protein may be implicated in the regulation of vascular contractility and blood pressure, probably by the impairment of NO production through H2O2-mediated epigenetic inhibition of eNOS expression.

  • DJ-1/park7
  • Vascular contractility
  • eNOS
  • Epigenetic modification
View Full Text

Sign in

ESC members If your subscription is provided via the European Society of Cardiology, either as a member or an ESC Congress delegate, select the 'ESC Member and Congress Delegate Sign In' link in the list below. Discover if you are an ESC member here.

Otherwise, if your subscription is via OUP, enter your OUP username and password, or select an alternative sign in option below.

List of OpenAthens registered sites, including contact details.