Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator Mediates the Angiogenic Response to Peripheral Ischemia in Mice With Type 2 Diabetes Mellitus Article Swipe
Tu Nguyen
,
Mei Zheng
,
Maura Knapp
,
Nikola Sladojević
,
Qin Zhang
,
Lizhuo Ai
,
Devin Harrison
,
Anna Chen
,
Albert Sitikov
,
Le Shen
,
Frank J. Gonzalez
,
Qiong Zhao
,
Yun Fang
,
James Liao
,
Rongxue Wu
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fcell.2021.691801
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3389/fcell.2021.691801
Hypoxia-inducible factors (HIFs) are the master regulators of angiogenesis, a process that is impaired in patients with diabetes mellitus (DM). The transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF1β) has been implicated in the development and progression of diabetes. Angiogenesis is driven primarily by endothelial cells (ECs), but both global and EC-specific loss of ARNT-cause are associated with embryonic lethality. Thus, we conducted experiments in a line of mice carrying an inducible, EC-specific ARNT-knockout mutation ( Arnt Δ EC, ERT2 ) to determine whether aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. Mice were first fed with a high-fat diet to induce diabetes. Arnt Δ EC, ERT2 mice were then adminstrated with oral tamoxifen to disrupt Arnt and peripheral angiogenesis was evaluated by using laser-Doppler perfusion imaging to monitor blood flow after hindlimb ischemia. The Arnt Δ EC, ERT2 mice had impaired blood flow recovery under both non-diabetic and diabetic conditions, but the degree of impairment was greater in diabetic animals. In addition, siRNA-mediated knockdown of ARNT activity reduced measurements of tube formation, and cell viability in human umbilical vein endothelial cells (HUVECs) cultured under high-glucose conditions. The Arnt Δ EC, ERT2 mutation also reduced measures of cell viability, while increasing the production of reactive oxygen species (ROS) in microvascular endothelial cells (MVECs) isolated from mouse skeletal muscle, and the viability of Arnt Δ EC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with an ROS inhibitor. Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice, and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production.
Related Topics
Concepts
Aryl hydrocarbon receptor nuclear translocator
Endocrinology
Angiogenesis
Internal medicine
Biology
Aryl hydrocarbon receptor
Medicine
Transcription factor
Biochemistry
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fcell.2021.691801
- OA Status
- gold
- Cited By
- 9
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3169964746
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3169964746Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fcell.2021.691801Digital Object Identifier
- Title
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Endothelial Aryl Hydrocarbon Receptor Nuclear Translocator Mediates the Angiogenic Response to Peripheral Ischemia in Mice With Type 2 Diabetes MellitusWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-06-10Full publication date if available
- Authors
-
Tu Nguyen, Mei Zheng, Maura Knapp, Nikola Sladojević, Qin Zhang, Lizhuo Ai, Devin Harrison, Anna Chen, Albert Sitikov, Le Shen, Frank J. Gonzalez, Qiong Zhao, Yun Fang, James Liao, Rongxue WuList of authors in order
- Landing page
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https://doi.org/10.3389/fcell.2021.691801Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
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https://doi.org/10.3389/fcell.2021.691801Direct OA link when available
- Concepts
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Aryl hydrocarbon receptor nuclear translocator, Endocrinology, Angiogenesis, Internal medicine, Biology, Aryl hydrocarbon receptor, Medicine, Transcription factor, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
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9Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 3, 2023: 4Per-year citation counts (last 5 years)
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54Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.production | 211 |
| abstract_inverted_index.regulators | 6 |
| abstract_inverted_index.suppressed | 262 |
| abstract_inverted_index.viability, | 207 |
| abstract_inverted_index.EC-specific | 55, 76 |
| abstract_inverted_index.aberrations | 88 |
| abstract_inverted_index.conditions, | 159 |
| abstract_inverted_index.conditions. | 195 |
| abstract_inverted_index.development | 38 |
| abstract_inverted_index.endothelial | 48, 189, 219, 256 |
| abstract_inverted_index.experiments | 67 |
| abstract_inverted_index.hydrocarbon | 24 |
| abstract_inverted_index.production. | 287 |
| abstract_inverted_index.progression | 40 |
| abstract_inverted_index.Angiogenesis | 43 |
| abstract_inverted_index.adminstrated | 119 |
| abstract_inverted_index.angiogenesis | 128 |
| abstract_inverted_index.deficiencies | 97 |
| abstract_inverted_index.high-glucose | 194, 237 |
| abstract_inverted_index.measurements | 178 |
| abstract_inverted_index.non-diabetic | 156 |
| abstract_inverted_index.observations | 251 |
| abstract_inverted_index.translocator | 27 |
| abstract_inverted_index.ARNT-knockout | 77 |
| abstract_inverted_index.Collectively, | 249 |
| abstract_inverted_index.angiogenesis, | 8 |
| abstract_inverted_index.laser-Doppler | 133 |
| abstract_inverted_index.microvascular | 218 |
| abstract_inverted_index.transcription | 21 |
| abstract_inverted_index.concentrations | 238 |
| abstract_inverted_index.cytoprotective | 271 |
| abstract_inverted_index.siRNA-mediated | 172 |
| abstract_inverted_index.Hypoxia-inducible | 0 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 95 |
| corresponding_author_ids | https://openalex.org/A5101437078 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 15 |
| corresponding_institution_ids | https://openalex.org/I40347166 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6899999976158142 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.67147014 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |