Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population

Curtis, Anne M.; Zhang, Lifeng; Medenilla, Elizabeth; Gui, Ming; Wilkinson, Patrick; Hu, Erding; Giri, Jay; Doraiswamy, Vijay; Gunda, Sampath; Burgert, Mark; Moore, Jonni S.; Edelberg, Jay M.; Mohler, Emile R.

doi:10.1002/cyto.b.20528

Cited by 28 publications

(31 citation statements)

References 48 publications

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“…Impaired mobilization or depletion of endothelial progenitor cells derived from bone marrow are involved in the pathogenesis of ED, and their circulating levels can also be used as a marker of ED [31][32][33][34]. A relationship between decreased levels of progenitor cells and increased levels of cell-derived microparticles has been demonstrated in T2D [33].…”

Section: Abbreviationsmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

2013

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■ AbstractType 2 diabetes (T2D) markedly increases the risk of cardiovascular disease. Endothelial dysfunction (ED), an early indicator of diabetic vascular disease, is common in T2D and independently predicts cardiovascular risk. Although the precise pathogenic mechanisms for ED in T2D remain unclear, at inception they probably involve uncoupling of both endothelial nitric oxide synthase activity and mitochondrial oxidative phosphorylation, as well as the activation of vascular nicotinamide adenine dinucleotide phosphate oxidase. The major contributing factors include dyslipoproteinemia, oxidative stress, and inflammation. Therapeutic interventions are designed to target these pathophysiological factors that underlie ED. Therapeutic interventions, including lifestyle changes, antiglycemic agents and lipid-regulating therapies, aim to correct hyperglycemia and atherogenic dyslipidemia and to improve ED. However, high residual cardiovascular risk is seen in both research and clinical practice settings. Well-designed studies of endothelial function in appropriately selected volunteers afford a good opportunity to test new therapeutic interventions, paving the way for clinical trials and utilization in the care of the diabetic patient. However, based on the results from a recent clinical trial, niacin should not be added to a statin in individuals with low high-density lipoprotein cholesterol and very well controlled low-density lipoprotein cholesterol.

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Section: Abbreviationsmentioning

confidence: 99%

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

2013

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“…11 Currently, the ratio of EMPs to EPCs is regarded as a quantitative and clinically feasible measurement of vascular dysfunction and cardiovascular risk in patients with diabetes. 13 One study indicated fluvastatin could decrease EMP release from human coronary artery endothelial cells. 14 15 At the end of this study, the number of peripheral cEPCs was significantly elevated in the 40-mg atorvastatin group in comparison with the 10-mg atorvastatin group.…”

Section: Baseline Characteristics Of Subjects Among the 3 Groupsmentioning

confidence: 99%

“…12 At present, the ratio of EMPs to EPCs is regarded as a quantitative and clinically feasible measurement of vascular dysfunction and cardiovascular risk in patients with diabetes. 13 A previous study demonstrated fluvastatin could decrease EMP release from human coronary artery endothelial cells. 14 Currently, stabilizing cellular membranes to decrease the release of EMPs is considered as a target of vascular therapy.…”

Section: Introductionmentioning

confidence: 97%

Effect of 40 mg Versus 10 mg of Atorvastatin on Oxidized Low‐Density Lipoprotein, High‐Sensitivity C‐Reactive Protein, Circulating Endothelial‐Derived Microparticles, and Endothelial Progenitor Cells in Patients With Ischemic Cardiomyopathy

Huang

Cheng

Xie

et al. 2012

Clinical Cardiology

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Background: There are few recent data to delineate the beyond lipids-decreased effect of statins and the effect of different doses of statins on endothelial-derived microparticles (EMPs) and circulating endothelial progenitor cells (EPCs) in patients with ischemic cardiomyopathy (ICM). Hypothesis: Statins might have the beyond lipids-decreased effect and there were different effects between different doses of statins on EMPs and circulating EPCs in patients with ICM. Methods: One hundred patients with ICM and 100 healthy examined people, who served as the normal control group, were recruited to this study. Patients were randomly divided into 2 groups: 10-mg atorvastatin group (n = 50) and 40-mg atorvastatin group (n = 50). All subjects were followed for 1 year. The levels of serum lipids, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein (hsCRP), circulating EPCs, and EMPs were examined in all subjects. The incidences of adverse reactions in the 2 study groups were determined. Results: At the beginning of this study, there were no significant differences in baseline characteristics between the 2 study groups. At the end of this study, the levels of total cholesterol, low-density lipoprotein, serum hsCRP, oxLDL, and circulating EMPs were significantly decreased; circulating EPCs were significantly increased in the 40-mg atorvastatin group compared to the 10-mg atorvastatin group, P < 0.05. The multivariate linear regression analysis indicated that receiving only 40 mg of atorvastatin had a significant effect on the levels of circulating EPCs (β = 0.252, P = 0.014). There were no significant differences in the adverse reactions between the 2 groups. Conclusions: Use of 40 mg of atorvastatin might decrease the levels of circulating EMPs and increase the number of circulating EPCs in patients with ICM in comparison with 10 mg of atorvastatin, and the effect might be independent of the decrease of lipids, oxLDL, and hsCRP. IntroductionStatins, serving as antiatherosclerosis drugs, can significantly decrease the rates of cardiovascular events in patients with coronary heart disease (CHD) and have been extensively administered in secondary prevention of CHD.

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“…T2DM was used as the disease model because of the high risk for vascular complications, and previous works have reported the pathological implications 33,34 and clinical utilities 35,36 of circulating MPs in T2DM patients. Interestingly, both immune MPs (LMPs and NMPs) were strongly correlated to established cardiovascular risk factors, including body mass index, carotid intima-media thickness and triglyceride levels (Po0.05, Po0.01 and Po0.001, respectively) in T2DM patients (Figure 5d), suggesting a link between inflammation and lipid metabolism in diabetes patients.…”

Section: Mps Separation Using Hidffmentioning

confidence: 99%

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

et al. 2017

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Efficient separation of sub-micrometer synthetic or biological components is imperative in particle-based drug delivery systems and purification of extracellular vesicles for point-of-care diagnostics. Herein, we report a novel phenomenon in spiral inertial microfluidics, in which the particle transient innermost distance (D inner ) varies with size during Dean vortices-induced migration and can be utilized for small microparticle (MP) separation; aptly termed as high-resolution Dean flow fractionation (HiDFF). The developed technology was optimized using binary bead mixtures (1-3 μm) to achieve~100-to 1000-fold enrichment of smaller particles. We demonstrated tunable size fractionation of polydispersed drug-loaded poly(lactic-co-glycolic acid) particles for enhanced drug release and anti-tumor effects. As a proof-of-concept for microvesicles studies, circulating extracellular vesicles/ MPs were isolated directly from whole blood using HiDFF. Purified MPs exhibited well-preserved surface morphology with efficient isolation within minutes as compared with multi-step centrifugation. In a cohort of type 2 diabetes mellitus subjects, we observed strong associations of immune cell-derived MPs with cardiovascular risk factors including body mass index, carotid intima-media thickness and triglyceride levels (Po0.05). Overall, HiDFF represents a key technological progress toward highthroughput, single-step purification of engineered or cell-derived MPs with the potential for quantitative MP-based health profiling. NPG Asia Materials (2017) 9, e434; doi:10.1038/am.2017.175; published online 29 September 2017 INTRODUCTIONEnabling technologies for continuous, size-based separation of submicrometer engineered or biological components are highly desirable in clinical applications, such as particle-based drug delivery systems 1 and the purification of extracellular vesicles in clinical diagnostics. 2 In microparticle fabrication, conventional 'bottom-up' self-assembly emulsification techniques yield a broad particle size distribution, which can affect the drug release kinetics and biotransport in blood. 3,4 Although well-controlled and monodisperse particles can be produced by 'top-down' approaches using specific lithographic techniques 5,6 and microfluidics, 7,8 microfabricated particles are prone to damage during mechanical harvesting, a problem further aggravated at the smaller/nanoscale level. Similarly, microfluidic synthesis of drug-loaded polymeric particles requires compatible drug/surfactant chemistry with additional steps to remove solvent prior use. Developing novel tools to achieve tunable size fractionation of polydispersed synthetic particles would enable optimal biodistribution and controlled drug release. Such technologies also facilitate physical isolation of smaller biological targets (o2 μm) including platelets, microbes and extracellular vesicles in a label-free manner for unbiased downstream analysis.

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Relationship of microparticles to progenitor cells as a measure of vascular health in a diabetic population

Cited by 28 publications

References 48 publications

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Endothelial Dysfunction in Diabetes: Pathogenesis, Significance, and Treatment

Effect of 40 mg Versus 10 mg of Atorvastatin on Oxidized Low‐Density Lipoprotein, High‐Sensitivity C‐Reactive Protein, Circulating Endothelial‐Derived Microparticles, and Endothelial Progenitor Cells in Patients With Ischemic Cardiomyopathy

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

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