Induction of Angiogenesis by Malarial Infection through Hypoxia Dependent Manner
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초록
Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infec- tion actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×106 parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors in- cluding VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tis- sues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in vari- ous tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia- induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.
Abstract
Malarial infection induces tissue hypoxia in the host through destruction of red blood cells. Tissue hypoxia in malarial infection may increase the activity of HIF1α through an intracellular oxygen-sensing pathway. Activation of HIF1α may also induce vascular endothelial growth factor (VEGF) to trigger angiogenesis. To investigate whether malarial infec- tion actually generates hypoxia-induced angiogenesis, we analyzed severity of hypoxia, the expression of hypoxia-related angiogenic factors, and numbers of blood vessels in various tissues infected with Plasmodium berghei. Infection in mice was performed by intraperitoneal injection of 2×106 parasitized red blood cells. After infection, we studied parasitemia and survival. We analyzed hypoxia, numbers of blood vessels, and expression of hypoxia-related angiogenic factors in- cluding VEGF and HIF1α. We used Western blot, immunofluorescence, and immunohistochemistry to analyze various tis- sues from Plasmodium berghei-infected mice. In malaria-infected mice, parasitemia was increased over the duration of infection and directly associated with mortality rate. Expression of VEGF and HIF1α increased with the parasitemia in vari- ous tissues. Additionally, numbers of blood vessels significantly increased in each tissue type of the malaria-infected group compared to the uninfected control group. These results suggest that malarial infection in mice activates hypoxia- induced angiogenesis by stimulation of HIF1α and VEGF in various tissues.
참고문헌 (24)
- Ng S, "Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro", Dis Model Mech, 7, pp.215~224 (2014)
- Hansen DS, "Inflammatory responses associated with the induction of cerebral malaria : lessons from experimental murine models", PLoS Pathog, 8, pp.e1003045~ (2012)
- Engwerda CR, "The importance of the spleen in malaria", Trends Parasitol, 21, pp.75~80 (2005)
- Deininger MH, "Angiogenic proteins in brains of patients who died with cerebral malaria", J Neuroimmunol, 142, pp.101~111 (2003)
- Muehlenbachs A, "Hypertension and maternal-fetal conflict during placental malaria", PLoS Med, 3, pp.e446~ (2006)
- de Souza JB, "Cerebral malaria : the contribution of studies in animal models to our understanding of immunopathogenesis", Microbes Infect, 4, pp.291~300 (2002)
- Basir R, "Plasmodium berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria", Iran J Parasitol, 7, pp.62~74 (2012)
- Craig AG, "The role of animal models for research on severe malaria", PLoS Pathog, 8, pp.e1002401~ (2012)
- Hall N, "A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses", Science, 307, pp.82~86 (2005)
- Risau W, "Mechanisms of angiogenesis", Nature, 386, pp.671~674 (1997)
- Banai S, "Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia : implications for coronary angiogenesis", Cardiovasc Res, 28, pp.1176~1179 (1994)
- Shweiki D, "Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis", Nature, 359, pp.843~845 (1992)
- Ema M, "A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development", Proc Natl Acad Sci USA, 94, pp.4273~4278 (1997)
- Hioki A, "Pathophysiology of hypoxia in mice infected with Plasmodium berghei", Parasitol Res, 73, pp.298~302 (1987)
- Canavese M, "Protective or pathogenic effects of vascular endothelial growth factor(VEGF)as potential biomarker in cerebral malaria", Pathog Glob Health, 108, pp.67~75 (2014)
- Furuta T, "Elevated levels of vascular endothelial growth factor(VEGF)and soluble vascular endothelial growth factor receptor(VEGFR)-2 in human malaria", Am J Trop Med Hyg, 82, pp.136~139 (2010)
- Kang YJ, "Trichinella spiralis infection induces beta-actin co-localized with thymosin beta4", Vet Parasitol, 187, pp.480~485 (2012)
- 윤가영, "Long interspersed element-1 open reading frame 1 protein expression profiles in ovarian cancers", Genes & Genomics, 39(10), pp.1157~1162 (2017), 한국유전학회[DOI]
- Wang D, "Immunohistochemistry in the evaluation of neovascularization in tumor xenografts", Biotech Histochem, 83, pp.179~189 (2008)
- Elias RM, "Oxidative stress and modification of renal vascular permeability are associated with acute kidney injury during P. berghei ANKA infection", PLoS One, 7, pp.e44004~ (2012)
- Boeuf P, "Placental hypoxia during placental malaria", J Infect Dis, 197, pp.757~765 (2008)
- Ataide R, "Malaria in pregnancy interacts with and alters the angiogenic profiles of the placenta", PLoS Negl Trop Dis, 9, pp.e0003824~ (2015)
- Yang Y, "Exosomes from Plasmodium-infected hosts inhibit tumor angiogenesis in a murine Lewis lung cancer model", Oncogenesis, 6, pp.e351~ (2017)
- Chen L, "Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity", PLoS One, 6, pp.e24407~ (2011)