Neoagarotetraose from Marine Red Algae Attenuates Hypertensive Vascular Remodeling by Targeting FoxO4 to Inhibit Mitochondrial Superoxide Generation.
NA4 may reduce oxidative stress and lower blood pressure in hypertensive rats, but its effects in humans are not established.
Where it sits
this study against the rest of the foxo4-dri (foxo4-d-retro-inverso) corpusSummary and findings
The study measured the effects of neoagarotetraose (NA4) on hypertensive vascular remodeling in spontaneously hypertensive rats (SHR) at doses of 200 or 250 mg/kg/day for 4 weeks. NA4 treatment resulted in reduced mitochondrial superoxide levels and blood pressure in SHR. The study identified FoxO4 as a target affected by NA4 treatment.
Abstract
Oxidative stress is a key driver of hypertensive vascular remodeling. Neoagarotetraose (NA4), a marine-derived oligosaccharide, possesses potent antioxidant activity, but its effects on hypertension remain unexplored. Here, we investigated the role of NA4 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and in SHR in vivo. NA4 treatment significantly reduced mitochondrial superoxide, H<sub>2</sub>O<sub>2</sub> levels, and NADPH oxidase activity in SHR-VSMCs and suppressed their hyperproliferation and migration. RNA-seq identified FoxO4 as a significantly downregulated target. FoxO4 overexpression enhanced ROS production and VSMC dysfunction, and these effects were reversed by NA4. In SHR, oral administration of NA4 (200 or 250 mg/kg/day) for 4 weeks lowered blood pressure, attenuated vascular remodeling, and reduced arterial FoxO4 expression and superoxide generation. Collectively, NA4 ameliorates hypertensive vascular remodeling, and molecular docking suggests a potential interaction between NA4 and the FoxO4-ROS axis, highlighting its potential as a functional food ingredient for hypertension management.
Background
Oxidative stress is known to contribute to hypertensive vascular remodeling, and neoagarotetraose (NA4) has demonstrated antioxidant properties. However, its specific effects on hypertension and related vascular changes had not been previously explored. Understanding NA4's role could provide insights into potential dietary interventions for hypertension management.
Methods
The study utilized spontaneously hypertensive rats (SHR) as the model, with NA4 administered orally at doses of 200 or 250 mg/kg/day for 4 weeks. The primary outcome measures included blood pressure reduction and assessment of mitochondrial superoxide levels, NADPH oxidase activity, and vascular smooth muscle cell (VSMC) behavior.
Results
NA4 treatment significantly reduced mitochondrial superoxide levels and NADPH oxidase activity in SHR-VSMCs. Furthermore, oral administration of NA4 lowered blood pressure in SHR, although specific numeric values for blood pressure reduction were not provided in the abstract.
Interpretation
The findings suggest that NA4 may influence oxidative stress pathways relevant to hypertension, particularly through its interaction with FoxO4. While the results show statistical significance, the clinical relevance remains uncertain without human data. Confounding factors include the use of animal models and the lack of detailed information on sample size and study design.
Key findings
- NA4 treatment significantly reduced mitochondrial superoxide levels in SHR-VSMCs.
- NA4 lowered blood pressure in SHR after 4 weeks of oral administration at doses of 200 or 250 mg/kg/day.
- NADPH oxidase activity was significantly suppressed in SHR-VSMCs treated with NA4.
- FoxO4 was identified as a significantly downregulated target in RNA-seq analysis.
- NA4 treatment suppressed hyperproliferation and migration of VSMCs.
Limitations
- animal model only, no human data
- sample size not reported
- short duration of 4 weeks
- not all numeric findings reported in abstract