Related Experiment Video
Updated: Mar 8, 2026
05:57
Author Spotlight: Exploring Huotan Jiedu Tongluo Decoction as an Antihypertensive Drug
Published on: May 17, 2024
1.3K
Uric Acid Induces Endothelial Dysfunction by Activating the HMGB1/RAGE Signaling Pathway
Wei Cai1, Xi-Mei Duan2, Ying Liu3
1Department of Endocrinology and Metabolism, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Medical Genetics and Cell Biology, Medical College of Nanchang University, Nanchang, Jiangxi 330006, China.
Biomed Research International
|January 25, 2017
Summary
High uric acid levels cause endothelial dysfunction by activating the HMGB1/RAGE pathway, leading to inflammation and reduced nitric oxide production. Blocking RAGE can prevent these harmful effects.
Area of Science:
- Cardiovascular Biology
- Endothelial Cell Function
- Inflammation Research
Background:
- Endothelial dysfunction is linked to inflammation and elevated uric acid (UA).
- High mobility group box chromosomal protein 1 (HMGB1) is an inflammatory cytokine implicated in endothelial dysfunction.
- The receptor for advanced glycation end products (RAGE) mediates inflammatory responses.
Purpose of the Study:
- To investigate the role of the HMGB1/RAGE signaling pathway in uric acid-induced endothelial dysfunction.
- To evaluate the effects of high UA concentrations on endothelial cells and related inflammatory markers.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were exposed to high UA concentrations (20 mg/dL).
- Assessed endothelial function, nitric oxide (NO) production, and expression of HMGB1, RAGE, NF-κB, inflammatory cytokines, and adhesion molecules.
- Investigated the effect of RAGE blockade on UA-induced changes.
Main Results:
- High UA inhibited endothelial nitric oxide synthase (eNOS) expression and NO production.
- UA increased intracellular and extracellular HMGB1, upregulated RAGE expression, and activated NF-κB.
- Blocking RAGE reversed UA-induced HMGB1/RAGE upregulation, NF-κB activation, and restored eNOS expression and NO production.
Conclusions:
- High uric acid induces endothelial dysfunction through the HMGB1/RAGE signaling pathway.
- Targeting the HMGB1/RAGE pathway may offer a therapeutic strategy for UA-related endothelial dysfunction.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
3.8K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
01:15Receptor Downregulation in MVBs
2.9K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.9K
01:28Nitric Oxide Signaling Pathway
6.5K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
6.5K
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
523
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
523
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
01:31Regulation of the Unfolded Protein Response
3.1K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K