Potential therapeutic action of nitrite in sickle cell disease

Redox Biology
Nadeem WajihDaniel B Kim-Shapiro

Abstract

Sickle cell disease is caused by a mutant form of hemoglobin that polymerizes under hypoxic conditions, increasing rigidity, fragility, calcium influx-mediated dehydration, and adhesivity of red blood cells. Increased red cell fragility results in hemolysis, which reduces nitric oxide (NO) bioavailability, and induces platelet activation and inflammation leading to adhesion of circulating blood cells. Nitric Oxide inhibits adhesion and platelet activation. Nitrite has emerged as an attractive therapeutic agent that targets delivery of NO activity to areas of hypoxia through bioactivation by deoxygenated red blood cell hemoglobin. In this study, we demonstrate anti-platelet activity of nitrite at doses achievable through dietary interventions with comparison to similar doses with other NO donating agents. Unlike other NO donating agents, nitrite activity is shown to be potentiated in the presence of red blood cells in hypoxic conditions. We also show that nitrite reduces calcium associated loss of phospholipid asymmetry that is associated with increased red cell adhesion, and that red cell deformability is also improved. We show that nitrite inhibits red cell adhesion in a microfluidic flow-channel assay after endothelial cell a...Continue Reading

Citations

Aug 29, 2018·British Journal of Pharmacology·Anthony W DeMartinoMark T Gladwin
Mar 10, 2018·Frontiers in Physiology·Christine C HelmsDaniel B Kim-Shapiro
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Nicola Conran, John D Belcher
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Camille FaesRafal Pawlinski
Mar 28, 2019·American Journal of Hematology·Jon A DetterichJohn C Wood
Jan 30, 2019·Experimental Biology and Medicine·Nicola Conran, Lidiane Torres
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Daniel B Kim-Shapiro, Mark T Gladwin
Dec 4, 2020·Nitric Oxide : Biology and Chemistry·Nadeem WajihDaniel Kim-Shapiro
Mar 25, 2019·The American Journal of Pathology·Junaid Ansari, Felicity N E Gavins
Apr 17, 2021·American Journal of Respiratory and Critical Care Medicine·Bradley A MaronErika B Rosenzweig
May 20, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jamie E MeeganLorraine B Ware

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Methods Mentioned

BETA
electron paramagnetic resonance
transgenic

Software Mentioned

DEANOate
imageJ
CellQuestsoftware

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