Significance of urinary 11-dehydro-thromboxane B2 in age-related diseases: Focus on atherothrombosis.

Abstract

Platelet activation plays a key role in atherogenesis and atherothrombosis. Biochemical evidence of increased platelet activation in vivo can be reliably obtained through non-invasive measurement of thromboxane metabolite (TXM) excretion. Persistent biosynthesis of TXA2 has been associated with several ageing-related diseases, including acute and chronic cardio-cerebrovascular diseases and cardiovascular risk factors, such as cigarette smoking, type 1 and type 2 diabetes mellitus, obesity, hypercholesterolemia, hyperhomocysteinemia, hypertension, chronic kidney disease, chronic inflammatory diseases. Given the systemic nature of TX excretion, involving predominantly platelet but also extraplatelet sources, urinary TXM may reflect either platelet cyclooxygenase-1 (COX-1)-dependent TX generation or COX-2-dependent biosynthesis by inflammatory cells and/or platelets, or a combination of the two, especially in clinical settings characterized by low-grade inflammation or enhanced platelet turnover. Although urinary 11-dehydro-TXB2 levels are largely suppressed with low-dose aspirin, incomplete TXM suppression by aspirin predicts the future risk of vascular events and death in high-risk patients and may identify individuals who might benefit from treatments that more effectively block in vivo TX production or activity. Several disease-modifying agents, including lifestyle intervention, antidiabetic drugs and antiplatelet agents besides aspirin have been shown to reduce TX biosynthesis. Taken together, these aspects may contribute to the development of promising mechanism-based therapeutic strategies to reduce the progression of atherothrombosis. We intended to critically review current knowledge on both the pathophysiological significance of urinary TXM excretion in clinical settings related to ageing and atherothrombosis, as well as its prognostic value as a biomarker of vascular events.

• Authors: Paola Simeone, Andrea Boccatonda, Rossella Liani, Francesca Santilli
• Journal: Ageing research reviews (Ageing Res Rev) Vol. 48 Pg. 51-78 (12 2018) ISSN: 1872-9649 [Electronic] England
• PMID: 30273676 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Platelet Aggregation Inhibitors
• Thromboxane B2
• 11-dehydro-thromboxane B2
• Cyclooxygenase 1
• PTGS1 protein, human
• Aspirin

Topics

• Aging (metabolism, pathology)
• Animals
• Aspirin (pharmacology, therapeutic use)
• Atherosclerosis (drug therapy, pathology, urine)
• Biomarkers (urine)
• Cyclooxygenase 1 (urine)
• Diabetes Mellitus, Type 2 (drug therapy, pathology, urine)
• Humans
• Hypertension (drug therapy, pathology, urine)
• Platelet Activation (drug effects, physiology)
• Platelet Aggregation Inhibitors (pharmacology, therapeutic use)
• Thrombosis (drug therapy, pathology, urine)
• Thromboxane B2 (analogs & derivatives, urine)