Nitric oxide
metaboliteNitric oxide produced by endothelial cells regulates vasodilation and suppresses platelet adhesion; reduced bioavailability reflects endothelial dysfunction and predisposes to thrombosis.
Pathway placement
Cascade stepEndothelial activation & erosion
Confidencehigh
RationaleEndothelial signaling and dysfunction marker; inhibits platelet activation.
Also acts inPlatelet activation, Vascular inflammation
Druggability
Not assessed (no mapped human gene target).
Type I vs Type II discrimination
ScoresShared / rises in both
R — rupture / Type-I67
C — confounder / Type-II56
A — assay feasibility42
E — evidence strength38
T1DI (composite)9
Specificity differential (R−C)+11.1
Confounder panel (Type-II drivers)
1sepsis / systemic inflammationmag 2
2anemia / acute blood lossmag 2
3hypovolemia / dehydrationn/a
4tachyarrhythmiamag 1
5hypoxemia / respiratory failuremag 2
6hypertensive emergencymag 2
7high-demand / peri-operative stressmag 1
Coverage: 6/7 confounders with evidence
Tier: deep-scored (abstract-extracted) · 12 supporting references. See the discrimination table for all markers.
Assay & specimen
Class-level default (no specific cleared assay)— generic method inferred from analyte class; confirm against a specific product insert before use.
Specimen
Serum, plasma or urine
Collection tube
Serum separator (gold/red-top, SST) · Lithium heparin (green-top) · Sterile urine container
Method / principle
LC-MS/MS (targeted metabolomics) or enzymatic colorimetric where available
Reagent / substrate
Stable-isotope-labeled internal standard (MS); or enzyme-coupled Trinder reagent
Platform
LC-MS/MS; some automated chemistry
Turnaround · availability
Send-out / research · Specialized / research
Literature evidence(22)
- Molecular determinants of thromboinflammatory activation in inflammatory bowel disease.Journal of molecular medicine (Berlin, Germany) · 2026 · PMID 42298010 · doi
- Thromboinflammation and hemolysis after pulsed field ablation with a pentaspline catheter: Clinical predictors, renal safety, and rhythm outcomes.Heart rhythm · 2026 · PMID 41554366 · doi
- Relationship between amino acid metabolism and inflammation in coronary heart disease (Review).International journal of molecular medicine · 2025 · PMID 40476584 · doi
- Platelet Function and Markers of Atherothrombotic Risk in Individuals With Parathyroid Disorders.The Journal of clinical endocrinology and metabolism · 2025 · PMID 40037625 · doi
- Epidemiological and Translational Study of Calprotectin and Atherosclerotic Cardiovascular Disease.JAMA cardiology · 2025 · PMID 40332890 · doi
- Cardioprotective and hypotensive mechanistic insights of hydroethanolic extract ofL. kernels in isoprenaline-induced cardiotoxicity based on metabolomics andelectrophysiological models.Frontiers in pharmacology · 2024 · PMID 38348351 · doi
- Metabolomics analysis delineates the therapeutic effects of hydroethanolic extract of Cucumis sativus L. seeds on hypertension and isoproterenol-induced myocardial infarction.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022 · PMID 35180666 · doi
- Positive Association of Plasma Trimethylamine-N-Oxide and Atherosclerosis in Patient with Acute Coronary Syndrome.Cardiovascular therapeutics · 2022 · PMID 36420057 · doi
- NOS1-mediated macrophage and endothelial cell interaction in the progression of atherosclerosis.Cell biology international · 2021 · PMID 33501735 · doi
- Omega-3 polyunsaturated fatty acid supplementation improves lipid metabolism and endothelial function by providing a beneficial eicosanoid-pattern in patients with acute myocardial infarction: A randomized, controlled trial.Clinical nutrition (Edinburgh, Scotland) · 2020 · PMID 33041091 · doi
- Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation.Life sciences · 2019 · PMID 31356907 · doi
- Erectile dysfunction as a predictor of two-year prognosis in acute myocardial infarction.Cardiology journal · 2017 · PMID 28150293 · doi
- The clinical significance of endocardial endothelial dysfunction.Medicina (Kaunas, Lithuania) · 2017 · PMID 29074341 · doi
- Role of interferon alpha in endothelial dysfunction: insights into endothelial nitric oxide synthase-related mechanisms.The American journal of the medical sciences · 2014 · PMID 24796291 · doi
- Oxidation and endothelial dysfunction biomarkers of atherosclerotic plaque instability. Studies of the vascular wall and blood.Bulletin of experimental biology and medicine · 2012 · PMID 22866304 · doi
- Platelet activation in essential hypertension: implications for antiplatelet treatment.American journal of hypertension · 2010 · PMID 20094035 · doi
- [Training after percutaneous coronary intervention- an undervalued treatment option?].Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke · 2007 · PMID 17519991
- [HIV infection, antiretroviral therapy, and endothelium].Herz · 2005 · PMID 16170677 · doi
- Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and cardioprotection.Seminars in thrombosis and hemostasis · 2005 · PMID 15852226 · doi
- C-reactive protein incites atherosclerosis.The Canadian journal of cardiology · 2004 · PMID 15309202
- Endothelial dysfunction in acute and chronic coronary syndromes: evidence for a pathogenetic role of oxidative stress.Archives of biochemistry and biophysics · 2003 · PMID 14654064 · doi
- Atherosclerosis-associated endothelial dysfunction.Zeitschrift fur Kardiologie · 2000 · PMID 11151799 · doi
Clinical trials(3)
- Nitric Oxide Inhalation Therapy for Myocardial Ischemia in Patients With Coronary Artery DiseaseNCT00014040 · PHASE2 · COMPLETED · Nitric Oxide and INOpulse Delivery System
- A Randomized, Double-Blind Trial to Test Higher- Versus Lower-Doses of Aspirin on Inflammatory Markers and Platelet Biomarkers and Nitric Oxide Formation & Endothelial Function in Secondary Prevention (Pts w/Chronic Stable Coronary Disease)NCT00272337 · PHASE4 · COMPLETED · Aspirin
- a Single Centre Open Pilot Study to Explore if the Efficacy of PLAtelet Aggregation Inhibition by Ticagrelor Mediated P2Y12 Blockade Dependent Upon Endogenous Endothelial Nitric OXide?NCT02169596 · PHASE4 · COMPLETED · Ticagrelor, EndoPAT - endothelial assessment