PMID- 17495224
OWN - NLM
STAT- MEDLINE
DCOM- 20070705
LR  - 20220316
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 100
IP  - 12
DP  - 2007 Jun 22
TI  - Heme oxygenase-1 expression in macrophages plays a beneficial role in 
      atherosclerosis.
PG  - 1703-11
AB  - Heme oxygenase (HO-1) is the rate-limiting enzyme in the catabolism of heme, 
      which leads to the generation of biliverdin, iron, and carbon monoxide. It has 
      been shown to have important antioxidant and antiinflammatory properties that 
      result in a vascular antiatherogenic effect. To determine whether HO-1 expression 
      in macrophages constitutes a significant component of the protective role in 
      atherosclerosis, we evaluated the effect of decreased or absent HO-1 expression 
      in peritoneal macrophages on oxidative stress and inflammation in vitro, and the 
      effect of complete deficiency of HO-1 expression in macrophages in 
      atherosclerotic lesion formation in vivo. We found that compared with HO-1(+/+) 
      controls, peritoneal macrophages from HO-1(-/-) and HO-1(+/-) mice exhibited (1) 
      increased reactive oxygen species (ROS) generation, (2) increased proinflammatory 
      cytokines such as monocyte chemotactic protein 1 (MCP-1) and interleukin 6 
      (IL-6), and (3) increased foam cell formation when treated with oxLDL, 
      attributable in part to increased expression of scavenger receptor A (SR-A). Bone 
      marrow transplantation experiments performed in lethally irradiated LDL-R null 
      female mice, reconstituted with bone marrow from HO-1(-/-) versus HO-1(+/+) mice, 
      revealed that HO-1(-/-) reconstituted animals exhibited atherosclerotic lesions 
      with a greater macrophage content as evaluated by immunohistochemistry and 
      planimetric assessment. We conclude that HO-1 expression in macrophages 
      constitutes an important component of the antiatherogenic effect by increasing 
      antioxidant protection and decreasing the inflammatory component of 
      atherosclerotic lesions.
FAU - Orozco, Luz D
AU  - Orozco LD
AD  - Department of Medicine, Division of Cardiology, David Geffen School of Medicine 
      at UCLA, Los Angeles, CA 90095, USA.
FAU - Kapturczak, Matthias H
AU  - Kapturczak MH
FAU - Barajas, Berenice
AU  - Barajas B
FAU - Wang, Xuping
AU  - Wang X
FAU - Weinstein, Michael M
AU  - Weinstein MM
FAU - Wong, Jack
AU  - Wong J
FAU - Deshane, Jessy
AU  - Deshane J
FAU - Bolisetty, Subhashini
AU  - Bolisetty S
FAU - Shaposhnik, Zory
AU  - Shaposhnik Z
FAU - Shih, Diana M
AU  - Shih DM
FAU - Agarwal, Anupam
AU  - Agarwal A
FAU - Lusis, Aldons J
AU  - Lusis AJ
FAU - Araujo, Jesus A
AU  - Araujo JA
LA  - eng
GR  - T32 HG002536/HG/NHGRI NIH HHS/United States
GR  - HL068157/HL/NHLBI NIH HHS/United States
GR  - HL30568/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070510
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, LDL)
RN  - 0 (Scavenger Receptors, Class A)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Atherosclerosis/*metabolism/pathology/*prevention & control
MH  - Bone Marrow Transplantation/pathology
MH  - Chemokine CCL2/metabolism
MH  - Foam Cells/pathology
MH  - Gene Expression Regulation
MH  - Gene Expression Regulation, Enzymologic
MH  - Heme Oxygenase-1/*metabolism
MH  - Interleukin-6/metabolism
MH  - Macrophages/*enzymology/pathology
MH  - Mice
MH  - Oxidative Stress/physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, LDL/genetics/physiology
MH  - Scavenger Receptors, Class A/genetics/physiology
EDAT- 2007/05/15 09:00
MHDA- 2007/07/06 09:00
CRDT- 2007/05/15 09:00
PHST- 2007/05/15 09:00 [pubmed]
PHST- 2007/07/06 09:00 [medline]
PHST- 2007/05/15 09:00 [entrez]
AID - CIRCRESAHA.107.151720 [pii]
AID - 10.1161/CIRCRESAHA.107.151720 [doi]
PST - ppublish
SO  - Circ Res. 2007 Jun 22;100(12):1703-11. doi: 10.1161/CIRCRESAHA.107.151720. Epub 
      2007 May 10.