Dietary inorganic nitrate mobilizes circulating angiogenic cells

Area of Science:

• Cardiovascular Research
• Nutritional Science
• Regenerative Medicine

Background:

• Nitric oxide (NO) is crucial for regulating circulating angiogenic cells (CACs).
• Dietary nitrate, found in vegetables, can be converted to nitrite and then NO in vivo, offering an alternative NO source.
• The role of inorganic dietary nitrate in CAC mobilization remains largely unexplored.

Purpose of the Study:

• To investigate the effect of inorganic dietary nitrate on the mobilization of CACs in healthy volunteers.
• To explore the underlying mechanisms involving the nitrate-nitrite-NO pathway and associated signaling molecules.

Main Methods:

• Randomized, double-blind, placebo-controlled study in healthy volunteers ingesting sodium nitrate or placebo.
• Quantification of CACs (CD34+/KDR+, CD133+/KDR+ cells) via flow cytometry.
• Measurement of plasma nitrite, nitrate, stem cell factor (SCF), and stromal cell-derived factor-1α (SDF-1α).
• Assessment of NOS-dependent vasodilation (flow-mediated dilation) and mechanistic studies in mice.

Main Results:

• Nitrate ingestion significantly increased plasma nitrite levels and acutely mobilized CD34+/KDR+ and CD133+/KDR+ CACs.
• Elevated levels of SCF and SDF-1α were observed, correlating with CAC mobilization.
• Nitrate intake enhanced NOS-dependent vasodilation, and NO-scavenging experiments in mice confirmed NO's role in nitrite-induced CAC mobilization.

Conclusions:

• Dietary inorganic nitrate acutely mobilizes CACs through a pathway involving sequential reduction to nitrite and NO.
• The nitrate-nitrite-NO pathway represents a novel nutritional strategy for modulating vascular regenerative processes.
• This finding has implications for leveraging dietary nitrate for therapeutic benefits in vascular health.