Chain-length dependent effects of inorganic polyphosphate on endothelial function and nucleotide pool

Abstract

Endothelial cells (ECs) are the first line that comes into contact with blood pathogens, pathogen-derived molecules, and factors that stimulate coagulation and inflammation. Inorganic polyphosphate (polyP) - a polymer of orthophosphate units synthesized by bacteria under stress and released by platelets upon their activation is among these factors. Bacterial and platelet polyPs differ in length, and both variants elicit different effects in eukaryotes. This study aimed to investigate how bacterial-like long-chain polyP (Lc-polyP) and platelet-like short-chain polyP (Sc-polyP) affect the functionality of cultured endothelial cells. Murine immortalized heart endothelial cells (H5V) were exposed to polyP of different chain lengths to assess the effects of these stimuli on intracellular energetics, permeability, and endothelial adhesion. We observed varying effects between Lc-polyP and Sc-polyP treatments. Lc-polyP more potently disturbs the intracellular ATP pool, a parameter strongly connected with vascular injury, whereas Sc-polyP robustly stimulates cellular adhesion to the endothelium. Both polymers similarly enhance endothelial permeability, suggesting potent immunomodulatory properties. This study provides evidence that polyP elicits profound cellular responses in endothelium depending on the polymer’s length.

Keywords:

• Inorganic polyphosphate (polyP)
• endothelium
• endothelial activation
• intracellular nucleotides
• extravasation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Science Centre of Poland (grant number: 2021/43/D/NZ4/02501).