Diesel exhaust exposure induces angiogenesis.
Our aim was to test the hypothesis that exposure to whole diesel exhaust (WDE) would enhance angiogenesis/vasculogenesis. Male apolipoprotein E-deficient mice, with either scaffold implantation subcutaneously or hindlimb ischemia, were exposed to either WDE (containing diesel exhaust particle [DEP] at a concentration of about 1mg/m(3)) or filtered air 6 h/day, 5 days/week in a whole body exposure chamber for 2, 5, or 8 weeks, respectively. WDE exposure significantly increased total cell counts in the scaffolds, aortic, and perivascular fat tissues. Macrophage infiltration was enhanced and CD31 expression increased in the scaffolds, which was coupled by increased alpha-smooth muscle actin (alpha-SMA) expression. WDE exposure led to increased CD31 expression, while decreasing endothelial nitric oxide synthase in the aortic wall. The vessel volume measured by micro-CT was increased in ischemic and non-ischemic hindlimbs in response to WDE exposure. DEP exposure induced capillary-like tube formation in endothelial cells in vitro, and caused capillary sprouting from aortic rings ex vivo. In addition, WDE exposure significantly increased mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, while decreasing prolylhydroxylase (PHD) 2 expression. WDE exposure increases inflammatory cell infiltration, enhances the vessel volume/flow, and increases capillary tube formation and sprouting, thereby inducing angiogenesis and vasculogenesis. The angiogenic effects may occur through increasing HIF-1alpha and VEGF while decreasing PHD2 expression.
Xu
Xiaohua
X
Division of Environmental Health Sciences, Colleges of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1240, USA.
Kherada
Nisharahmed
N
Hong
Xinru
X
Quan
Chunli
C
Zheng
Ling
L
Wang
Aixia
A
Wold
Loren E
LE
Lippmann
Morton
M
Chen
Lung Chi
LC
Rajagopalan
Sanjay
S
Sun
Qinghua
Q
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005263:Femoral Artery / Q000502:physiology; D005268:Femoral Vein / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply / Q000502:physiology; D000860:Hypoxia / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007511:Ischemia; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000502:physiology; D012039:Regional Blood Flow; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D001335:Vehicle Emissions / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D001057:Apolipoproteins E; D004396:Coloring Agents; D001335:Vehicle Emissions
Nat Med. 2003 Jun;9(6):677-84
12778166
Inhal Toxicol. 2009 Jan;21(1):48-54
18923949
Environ Health Perspect. 2004 Sep;112(13):1307-12
15345344
Int J Cancer. 2004 Sep 20;111(5):647-52
15252832
JAMA. 2002 Mar 6;287(9):1132-41
11879110
Occup Environ Med. 2007 Jun;64(6):373-9
17182639
Circ Res. 1999 Aug 6;85(3):221-8
10436164
Cancer Cell. 2003 Sep;4(3):191-6
14522253
Environ Health Perspect. 2002 Apr;110(4):349-53
11940452
Exp Biol Med (Maywood). 2006 Nov;231(10):1626-32
17060683
Circulation. 2005 Jun 7;111(22):2913-20
15927967
Curr Med Chem. 2007;14(17):1853-62
17627521
Nature. 2000 Sep 14;407(6801):249-57
11001068
Mol Cell Biol. 1996 Sep;16(9):4604-13
8756616
J Pathol. 2000 Feb;190(3):338-42
10685067
Cardiovasc Res. 2003 May 1;58(2):378-89
12757872
Environ Sci Technol. 2004 May 1;38(9):2513-22
15180045
N Engl J Med. 2007 Dec 6;357(23):2348-58
18057337
J Mol Cell Cardiol. 2004 Jan;36(1):25-32
14734044
Circulation. 2003 Mar 4;107(8):1202-8
12615802
Nat Rev Mol Cell Biol. 2004 May;5(5):343-54
15122348
Pharm Res. 2005 Jul;22(7):1110-6
16028011
Nature. 2000 Sep 14;407(6801):242-8
11001067
Mutat Res. 2009 Mar 31;674(1-2):45-54
19013537
Lancet Oncol. 2009 May;10(5):453-4
19418618
Circulation. 2004 Jun 1;109(21):2655-71
15173049
Environ Health Perspect. 2000 Aug;108 Suppl 4:743-50
10931793
Microcirculation. 2003 Jan;10(1):83-97
12610665
Clin Occup Environ Med. 2006;5(4):797-815
17110293
N Engl J Med. 2007 Feb 1;356(5):447-58
17267905
Inhal Toxicol. 2004 Apr;16(4):177-93
15204765
Environ Health Perspect. 2000 Oct;108(10):941-7
11049813
Nat Med. 2003 Jun;9(6):653-60
12778163
Science. 2007 Oct 5;318(5847):62-4
17916722