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- Title
Glycyrrhizic Acid Inhibits High-Mobility Group Box-1 and Homocysteine-Induced Vascular Dysfunction.
- Authors
Gadanec, Laura Kate; Andersson, Ulf; Apostolopoulos, Vasso; Zulli, Anthony
- Abstract
Hyperhomocysteinemia (HHcy) worsens cardiovascular outcomes by impairing vascular function and promoting chronic inflammation via release of danger-associated molecular patterns, such as high-mobility group box-1 (HMGB-1). Elevated levels of HMGB-1 have recently been reported in patients with HHcy. Therefore, targeting HMGB-1 may be a potential therapy to improve HHcy-induced cardiovascular pathologies. This study aimed to further elucidate HMGB-1′s role during acute HHcy and HHcy-induced atherogenesis and to determine if inhibiting HMGB-1 with glycyrrhizic acid (Glyz) improved vascular function. Male New Zealand White rabbits (n = 25) were placed on either a standard control chow (CD; n = 15) or atherogenic diet (AD; n = 10) for 4 weeks. Rabbit serum and Krebs taken from organ bath studies were collected to quantify HMGB-1 levels. Isometric tension analysis was performed on abdominal aorta (AA) rings from CD and AD rabbits. Rings were incubated with homocysteine (Hcy) [3 mM] for 60 min to induce acute HHcy or rhHMGB-1 [100 nM]. Vascular function was assessed by relaxation to cumulative doses of acetylcholine. Markers of vascular dysfunction and inflammation were quantified in the endothelium, media, and adventitia of AA rings. HMGB-1 was significantly upregulated in serum (p < 0.0001) and Krebs (p < 0.0001) after Hcy exposure or an AD. Incubation with Hcy (p < 0.0001) or rhHMGB-1 (p < 0.0001) and an AD (p < 0.0001) significantly reduced relaxation to acetylcholine, which was markedly improved by Glyz. HMGB-1 expression was elevated (p < 0.0001) after Hcy exposure and AD (p < 0.0001) and was normalized after Glyz treatment. Moreover, markers of vascular function, cell stress and inflammation were also reduced after Glyz. These results demonstrate that HMGB-1 has a central role during HHcy-induced vascular dysfunction and inhibiting it with Glyz could be a potential treatment option for cardiovascular diseases.
- Subjects
HOMOCYSTEINE; BIOMARKERS; STATISTICS; CATHELICIDINS; ANALYSIS of variance; INFLAMMATION; ANIMAL experimentation; IMMUNOHISTOCHEMISTRY; ONE-way analysis of variance; RABBITS; HYDROCARBONS; ACETYLCHOLINE; ATHEROSCLEROSIS; T-test (Statistics); DIET therapy for heart diseases; ENZYME-linked immunosorbent assay; DATA analysis; HYPERHOMOCYSTEINEMIA; PHARMACODYNAMICS; DISEASE complications
- Publication
Nutrients, 2023, Vol 15, Issue 14, p3186
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu15143186