Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus

Abstract

Background— Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control. Methods and Results— Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls ( P =0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells ( P =0.045), granulocytes ( P =0.004), and platelets ( P =0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor-α and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro ( P =0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F 1+2 and thrombin-antithrombin complexes. Conclusions— TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.

Microparticles as Biomarkers of Vascular Dysfunction in Metabolic Syndrome and its Individual Components

“…For instance, platelet-derived microparticles are positively associated with abnormal carotid and intima-media thickness and body mass index in obese patients [21]. In addition, microparticles from platelets positively correlate with plasma glucose and insulin levels whereas microparticles from T-helper cells positively and negatively correlate with body mass index (BMI) and HDL-cholesterol, respectively [12].…”

“…However, this hypothesis has been little studied. Thus, circulating levels of microvesicles from platelets [11] and tissue-factor-positive microvesicles from T cells or neutrophils [12] negatively correlate with plasma HDL levels. Finally, with regard to microparticle composition, it has been reported that microparticles envelope and protect mRNA and miRNA from extracellular ribonuclease degradation and in this way represent veritable cargo allowing intercellular communication [13].…”

Hemostatic abnormalities in endocrine and metabolic disorders

“…VLDL can also up-regulate PAI-1 gene expression, thus increasing the PAI-1 concentration and activity in plasma -a process that is strongly associated with increased platelet aggregation and clot formation (120)(121)(122)(123)(124)(125)136). Finally, it has also been shown that the amount of platelet microparticles, small membrane vesicles that support the coagulation by exposure of anionic phospholipids and TF, is closely associated with the increasing number of the components of the metabolic syndrome (137).…”

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

“…In addition to coagulation and vascular inflammation, numerous studies indicate that MVs are also involved in angiogen- [81] . Tsimerman et al found that incubation of HUVECs with MVs from patients with severe diabetic foot ulcers could induce the formation of stable and branched networks [35] , suggesting the key role of MVs in angiogenesis and the skin wound healing process in diabetes.…”