Inducible Nitric Oxide Synthase in Circulating Microvesicles: Discovery, Evolution, and Evidence as a Novel Biomarker and the Probable Causative Agent for Sepsis

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Abstract
Background: The sepsis pathology remains an enormous medical problem globally because morbidity and mortality remain unacceptably high in septic patients despite intense research efforts. The economic and societal burden of sepsis makes it the most pressing patient care issue in the US and worldwide. Sepsis is a dysregulated immune response normally initiated by an infection. The need for an early, accurate, and reliable biomarker test to detect the onset of sepsis and for a targeted sepsis therapy is widely recognized in the biomedical community. Content: This report reviews the published findings relevant to microvesicle-associated inducible nitric oxide synthase (MV-A iNOS) as a novel plasma biomarker for the onset of sepsis, including human clinical studies and animal studies. Plasma iNOS as both a standalone test and 1 of the components of a novel panel of biomarkers to stage the progression of sepsis is presented and discussed in comparison with other biomarkers and other proposed panels of biomarkers for sepsis. Summary: The data strongly support the concept that extracellular plasma MV-A iNOS in circulating microvesicles is centrally involved in the initiation of sepsis, and a diagnostic test based on plasma iNOS can serve as an early presymptomatic warning signal for the onset of sepsis. A novel panel of plasma biomarkers comprising iNOS, pro-interleukin-18, pro-interleukin-33, and regenerating protein 1-α is proposed as a multianalyte presymptomatic method to stage the onset of sepsis for improved, prompt, data-driven patient care.
Funding Information
  • National Institute of General Medical Sciences
  • National Institutes of Health (R43GM58964, R44GM58964, RC3GM093717)

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