HtrA1 alters endothelial tube formation characteristics in an in vitro model

Harmeet Singh, Guiying Nie

Research output: Other contributionOther

Abstract

High temperature requirement factor A1 (HtrA1) is a serine protease of the mammalian HtrA family. It is ubiquitously expressed with high levels in the placenta. Dysregulation of HtrA1 has been linked to a number of diseases, in particular age-related macular degeneration (AMD) and preeclampsia (PE) in which HtrA1 is significantly increased. AMD is the leading cause of irreversible visual impairment in older people, affecting millions across the globe. PE is a life-threatening pregnancy complication, affecting 2- 7% of pregnant women worldwide. Although AMD and PE are very different diseases, both are associated with endothelial dysfunction and dysregulation of angiogenesis. Given HtrA1 is up-regulated in both AMD and PE, in this study we examined the impact of excessive HtrA1 on capillary tube formation of HUVECs as an in vitro angiogenesis model. HtrA1 at high concentrations significantly increased the total number of tube branch points and inter-tubular loops, but considerably decreased the mean tube length, resulting in more but much smaller tubes. However, these smaller tubes were incomplete/broken. These data demonstrated that high concentrations of HtrA1 altered endothelial tube formation characteristics of HUVEVs. Our results suggest that HtrA1 over-expression in AMD and PE may directly contribute to the endothelial dysfunction in these diseases.
Original languageEnglish
PublisherbioRxiv
Number of pages15
DOIs
Publication statusAccepted/In press - 2019

Cite this

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title = "HtrA1 alters endothelial tube formation characteristics in an in vitro model",
abstract = "High temperature requirement factor A1 (HtrA1) is a serine protease of the mammalian HtrA family. It is ubiquitously expressed with high levels in the placenta. Dysregulation of HtrA1 has been linked to a number of diseases, in particular age-related macular degeneration (AMD) and preeclampsia (PE) in which HtrA1 is significantly increased. AMD is the leading cause of irreversible visual impairment in older people, affecting millions across the globe. PE is a life-threatening pregnancy complication, affecting 2- 7{\%} of pregnant women worldwide. Although AMD and PE are very different diseases, both are associated with endothelial dysfunction and dysregulation of angiogenesis. Given HtrA1 is up-regulated in both AMD and PE, in this study we examined the impact of excessive HtrA1 on capillary tube formation of HUVECs as an in vitro angiogenesis model. HtrA1 at high concentrations significantly increased the total number of tube branch points and inter-tubular loops, but considerably decreased the mean tube length, resulting in more but much smaller tubes. However, these smaller tubes were incomplete/broken. These data demonstrated that high concentrations of HtrA1 altered endothelial tube formation characteristics of HUVEVs. Our results suggest that HtrA1 over-expression in AMD and PE may directly contribute to the endothelial dysfunction in these diseases.",
author = "Harmeet Singh and Guiying Nie",
year = "2019",
doi = "10.1101/539304",
language = "English",
publisher = "bioRxiv",
type = "Other",

}

HtrA1 alters endothelial tube formation characteristics in an in vitro model. / Singh, Harmeet; Nie, Guiying.

15 p. bioRxiv. 2019, .

Research output: Other contributionOther

TY - GEN

T1 - HtrA1 alters endothelial tube formation characteristics in an in vitro model

AU - Singh, Harmeet

AU - Nie, Guiying

PY - 2019

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N2 - High temperature requirement factor A1 (HtrA1) is a serine protease of the mammalian HtrA family. It is ubiquitously expressed with high levels in the placenta. Dysregulation of HtrA1 has been linked to a number of diseases, in particular age-related macular degeneration (AMD) and preeclampsia (PE) in which HtrA1 is significantly increased. AMD is the leading cause of irreversible visual impairment in older people, affecting millions across the globe. PE is a life-threatening pregnancy complication, affecting 2- 7% of pregnant women worldwide. Although AMD and PE are very different diseases, both are associated with endothelial dysfunction and dysregulation of angiogenesis. Given HtrA1 is up-regulated in both AMD and PE, in this study we examined the impact of excessive HtrA1 on capillary tube formation of HUVECs as an in vitro angiogenesis model. HtrA1 at high concentrations significantly increased the total number of tube branch points and inter-tubular loops, but considerably decreased the mean tube length, resulting in more but much smaller tubes. However, these smaller tubes were incomplete/broken. These data demonstrated that high concentrations of HtrA1 altered endothelial tube formation characteristics of HUVEVs. Our results suggest that HtrA1 over-expression in AMD and PE may directly contribute to the endothelial dysfunction in these diseases.

AB - High temperature requirement factor A1 (HtrA1) is a serine protease of the mammalian HtrA family. It is ubiquitously expressed with high levels in the placenta. Dysregulation of HtrA1 has been linked to a number of diseases, in particular age-related macular degeneration (AMD) and preeclampsia (PE) in which HtrA1 is significantly increased. AMD is the leading cause of irreversible visual impairment in older people, affecting millions across the globe. PE is a life-threatening pregnancy complication, affecting 2- 7% of pregnant women worldwide. Although AMD and PE are very different diseases, both are associated with endothelial dysfunction and dysregulation of angiogenesis. Given HtrA1 is up-regulated in both AMD and PE, in this study we examined the impact of excessive HtrA1 on capillary tube formation of HUVECs as an in vitro angiogenesis model. HtrA1 at high concentrations significantly increased the total number of tube branch points and inter-tubular loops, but considerably decreased the mean tube length, resulting in more but much smaller tubes. However, these smaller tubes were incomplete/broken. These data demonstrated that high concentrations of HtrA1 altered endothelial tube formation characteristics of HUVEVs. Our results suggest that HtrA1 over-expression in AMD and PE may directly contribute to the endothelial dysfunction in these diseases.

U2 - 10.1101/539304

DO - 10.1101/539304

M3 - Other contribution

PB - bioRxiv

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