Endothelial arginase II: a novel target for the treatment of atherosclerosis.

Abstract:

:Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. In ApoE(-/-) mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II(-/-) mice) prevents high-cholesterol diet-dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein-dependent increases in vascular stiffness. Furthermore, arginase inhibition significantly decreases plaque burden. These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis.

journal_name

Circ Res

journal_title

Circulation research

authors

Ryoo S,Gupta G,Benjo A,Lim HK,Camara A,Sikka G,Lim HK,Sohi J,Santhanam L,Soucy K,Tuday E,Baraban E,Ilies M,Gerstenblith G,Nyhan D,Shoukas A,Christianson DW,Alp NJ,Champion HC,Huso D,Berkowitz DE

doi

10.1161/CIRCRESAHA.107.169573

subject

Has Abstract

pub_date

2008-04-25 00:00:00

pages

923-32

issue

8

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.107.169573

journal_volume

102

pub_type

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