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Microparticles as new markers of cardiovascular risk in diabetes and beyond
Francesca Santilli, Marco Marchisio, Paola Lanuti
1Prof. Giovanni Davì, Center of Excellence on Aging, "G. D'Annunzio" University Foundation, Via Colle dell'Ara, 66013 Chieti, Italy, Tel.: +39 0871 541312, Fax: +39 0871 541261,
Abstract:
The term microparticle (MP) identifies a heterogeneous population of vesicles playing a relevant role in the pathogenesis of vascular diseases, cancer and metabolic diseases such as diabetes mellitus. MPs are released by virtually all cell types by shedding during cell growth, proliferation, activation, apoptosis or senescence processes. MPs, in particular platelet- and endothelial-derived MPs (PMPs and EMPs), are increased in a wide range of thrombotic disorders, with an interesting relationship between their levels and disease pathophysiology, activity or progression. EMP plasma levels have been associated with several cardiovascular diseases and risk factors. PMPs are also shown to be involved in the progressive formation of atherosclerotic plaque and development of arterial thrombosis, especially in diabetic patients. Indeed, diabetes is characterised by an increased procoagulant state and by a hyperreactive platelet phenotype, with enhanced adhesion, aggregation, and activation. Elevated MP levels, such as TF+ MPs, have been shown to be one of the procoagulant determinants in patients with type 2 diabetes mellitus. Atherosclerotic plaque constitutes an opulent source of sequestered MPs, called "plaque" MPs. Otherwise, circulating MPs represent a TF reservoir, named "blood-borne" TF, challenging the dogma that TF is a constitutive protein expressed in minute amounts. "Blood-borne" TF is mainly harboured by PMPs, and it can be trapped within the developing thrombus. MP detection and enumeration by polychromatic flow cytometry (PFC) have opened interesting perspectives in clinical settings, particularly for the evaluation of MP numbers and phenotypes as independent marker of cardiovascular risk, disease and outcome in diabetic patients.
Insights
Microparticles (MPs), particularly platelet- and endothelial-derived MPs, are elevated in vascular diseases and diabetes. Their levels, especially TF+ MPs, serve as crucial markers for cardiovascular risk and disease progression in diabetic patients.
Area of Science:
- Vascular Biology and Thrombosis
- Metabolic Diseases and Diabetes
- Cellular Vesicle Biology
Background:
- Microparticles (MPs) are vesicles shed by cells, implicated in vascular diseases, cancer, and diabetes.
- Elevated platelet- and endothelial-derived MPs (PMPs and EMPs) are linked to thrombotic disorders and cardiovascular disease.
- Diabetes mellitus is associated with a procoagulant state and hyperreactive platelets, increasing MP levels.
Purpose of the Study:
- To explore the role of microparticles (MPs) in the pathogenesis of vascular and metabolic diseases.
- To investigate the association between MP levels and cardiovascular risk, disease activity, and outcomes in diabetic patients.
- To highlight the significance of circulating MPs, particularly TF+ MPs, as a 'blood-borne' TF reservoir.
Main Methods:
- Utilized polychromatic flow cytometry (PFC) for MP detection and enumeration.
- Analyzed plasma levels of MPs, focusing on PMPs and EMPs.
- Investigated the presence and role of tissue factor (TF) within circulating MPs.
Main Results:
- Increased levels of MPs, including TF+ MPs, are observed in patients with type 2 diabetes mellitus.
- MPs, especially PMPs, contribute to atherosclerotic plaque formation and arterial thrombosis in diabetic patients.
- Circulating MPs, particularly PMPs, act as a significant source of 'blood-borne' tissue factor.
Conclusions:
- MP enumeration and phenotyping by PFC offer valuable clinical insights.
- MP levels are independent markers of cardiovascular risk, disease, and outcomes in diabetic individuals.
- MPs play a critical role in the procoagulant state associated with diabetes and vascular pathology.
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