title: Diesel exhaust exposure induces angiogenesis.
abstract: 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.
authors.affiliation: Division of Environmental Health Sciences, Colleges of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1240, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.forename: Nisharahmed
authors.initials: N
authors.lastname: Kherada
authors.forename: Xinru
authors.initials: X
authors.lastname: Hong
authors.forename: Chunli
authors.initials: C
authors.lastname: Quan
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Aixia
authors.initials: A
authors.lastname: Wang
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.forename: Morton
authors.initials: M
authors.lastname: Lippmann
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
mesh_terms: 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*
chemical_list: D000395:Air Pollutants, Occupational; D001057:Apolipoproteins E; D004396:Coloring Agents; D001335:Vehicle Emissions
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