NAD⁺ Enhancer Nicotinamide Riboside Alters Extracellular Purine Metabolism in Human Endothelial Cells

Area of Science:

• Biochemistry
• Cell Biology
• Vascular Biology

Background:

• Nicotinamide adenine dinucleotide (NAD⁺) is vital for cellular homeostasis and endothelial function.
• NAD⁺ depletion contributes to cardiovascular disorders.
• The role of Nicotinamide riboside (NR) in endothelial NAD⁺ restoration and its impact on purinergic signaling and immune cell adhesion requires further elucidation.

Purpose of the Study:

• To investigate the effects of NR on intracellular nucleotides, extracellular adenine nucleotide catabolism, and endothelial cell adhesive properties.
• To explore the molecular mechanisms underlying NR's beneficial effects on endothelial cells.

Main Methods:

• Cultured murine (H5V) and human (HMEC-1) microvascular endothelial cell lines were treated with NR.
• Intracellular NAD⁺ concentrations and cellular energy status were measured.
• Extracellular ATP and AMP hydrolysis rates, and adenosine deamination rates were assessed.
• CD73 activity and immune cell adhesion (T-lymphocytes, monocytes, platelets) to endothelial monolayers were analyzed.

Main Results:

• NR treatment significantly increased intracellular NAD⁺ levels in endothelial cells without altering their energy status.
• NR accelerated the extracellular hydrolysis of ATP and AMP.
• NR decreased the rate of adenosine deamination and enhanced CD73 activity.
• NR treatment led to reduced adhesion of T-lymphocytes, monocytes, and platelets to the endothelial monolayer.

Conclusions:

• Nicotinamide riboside (NR) acts as an effective intracellular NAD⁺ booster in endothelial cells.
• NR modulates extracellular nucleotide metabolism, favoring the formation of cytoprotective adenosine.
• These effects contribute to maintaining endothelial homeostasis and reducing inflammatory cell adhesion, highlighting a novel role for NR in vascular health.