ArticleHypertension research : official journal of the Japanese Society of Hypertension2015
Bilirubin exerts pro-angiogenic property through Akt-eNOS-dependent pathway.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Transcriptomic and Proteomic Changes in the Brain Along with Increasing Phenotypic Severity in a Rat Model of Neonatal Hyperbilirubinemia.International journal of molecular sciences · 2025Article
- Canagliflozin Inhibits Human Endothelial Cell Inflammation through the Induction of Heme Oxygenase-1.International journal of molecular sciences · 2022Article
- Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?Frontiers in physiology · 2020Review
- Beyond a Measure of Liver Function-Bilirubin Acts as a Potential Cardiovascular Protector in Chronic Kidney Disease Patients.International journal of molecular sciences · 2018Review
- Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases.International journal of molecular sciences · 2018Review
- Bilirubin, a new therapeutic for kidney transplant?Transplantation reviews (Orlando, Fla.) · 2018Review
- Bilirubin Is Inversely Associated With Cardiovascular Disease Among HIV-Positive and HIV-Negative Individuals in VACS (Veterans Aging Cohort Study).Journal of the American Heart Association · 2018Observational
- Heme oxygenase-1 is a potent inhibitor of placental ischemia-mediated endothelin-1 production in cultured human glomerular endothelial cells.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Inverse Relationship Between Serum Bilirubin Levels and Diabetic Foot in Chinese Patients with Type 2 Diabetes Mellitus.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Antiangiogenic Effects of VH02, a Novel Urea Derivative: In Vitro and in Vivo Studies.Molecules (Basel, Switzerland) · 2016Article
- Heme oxygenase-1-derived bilirubin counteracts HIV protease inhibitor-mediated endothelial cell dysfunction.Free radical biology & medicine · 2016Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.
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