Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players

Alexandru, Nicoleta; Bădilă, Elisabeta; Weiss, Emma; Cochior, Daniel; Stępień, Ewa; Georgescu, Adelina

doi:10.1016/j.bbrc.2016.02.038

Cited by 68 publications

(73 citation statements)

References 131 publications

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“…Diabetic encephalopathy, an important complication of diabetes, increases the probability of cognitive decline, acceleration of Alzheimer's disease and other forms of dementia (Summers, 2004; Pasquier et al, 2006). Such clinical outcomes in DM are multifactorial and are related to both macrovascular changes and microvascular injury due endothelial dysfunction leading to end-organ pathology (Alexandru et al, 2016). Substantial evidence from recent clinical and experimental studies suggests that prolonged hyperglycemic conditions, particularly in DM type 2, lead to the progressive impairment of neuronal function in the brain (Mooradian, 1997).…”

Section: Introductionmentioning

confidence: 99%

Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition

Bogush

Heldt

Persidsky

2017

J Neuroimmune Pharmacol

116

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Diabetes mellitus (DM) is a disorder due to the inability properly to metabolize glucose associated with dysregulation of metabolic pathways of lipids and proteins resulting in structural and functional changes of various organ systems. DM has detrimental effects on the vasculature, resulting in the development of various cardiovascular diseases and stemming from microvascular injury. The blood brain barrier (BBB) is a highly specialized structure protecting the unique microenvironment of the brain. Endothelial cells, connected by junctional complexes and expressing numerous transporters, constitute the main cell type in the BBB. Other components, including pericytes, basement membrane, astrocytes and perivascular macrophages, join endothelial cells to form the neurovascular unit (NVU) and contribute to the proper function and integrity of the BBB. The role of the BBB in the pathogenesis of diabetic encephalopathy and other diabetes-related complications in the central nervous system is apparent. However, the mechanisms, timing and consequences of BBB injury in diabetes are not well understood. The importance of further studies related to barrier dysfunction in diabetes is dictated by its potential involvement in the cognitive demise associated with DM. This review summarizes the impact of DM on BBB/NVU integrity and function leading to neurological and cognitive complications.

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Section: Introductionmentioning

confidence: 99%

Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition

Bogush

Heldt

Persidsky

2017

J Neuroimmune Pharmacol

116

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“…As a derivate of cellular membrane MPs are discussed powerful autocrine and paracrine transducer of structure and functions of the target cells. MP released by apoptotic endothelial cells posse a wide spectrum of biological effects on cell-to-cell communication by transferring a wide spectrum of active molecules (proteins, peptides, hormones, growth factors, microRNAs) exhibiting coagulation activity, mediating cell growth and tissue differentiation [10]. Additionally, apoptotic endothelial cell-derived MPs (EMPs) may directly injury an endothelial wall integrity and vascular function playing a central role in development of microvascular inflammation and IR [11].…”

Section: Introductionmentioning

confidence: 99%

“…The proportion of these components as well as an entire secretome is under a tight control of autocrine/paracrine mechanisms and inflammatory factors (i.e. tumor necrosis factoralpha, interleukin-2, -6), which induces EMP formation in a timedependent manner [9,10,25]. Consequently, the final reply of the recipient cells, such as endothelial progenitor cells, is depends on epigenetic regulation of secretome secretion and primary trigger, which affects vesiculation of target cells [10].…”

Section: Introductionmentioning

confidence: 99%

“…tumor necrosis factoralpha, interleukin-2, -6), which induces EMP formation in a timedependent manner [9,10,25]. Consequently, the final reply of the recipient cells, such as endothelial progenitor cells, is depends on epigenetic regulation of secretome secretion and primary trigger, which affects vesiculation of target cells [10]. Obviously, an ability of apoptotic EMPs to enhance and modulate several immune and inflammatory processes, coagulation and vascular function, angiogenesis and vascular injury, neovascularization and endothelial reparation may interact with other regulatory mechanisms the role of witch in the pathogenesis of abdominal obesity requires still being determined more pretty accurate.…”

Section: Introductionmentioning

confidence: 99%

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Biosensing of Circulating Apoptotic Endothelial Cell Micro particles: The Impact in Risk Stratification of Obesity

Berezin¹

2017

JABB

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Obesity is considered a main factor mediating a risk of diabetes mellitus development and a predictor of CV disease and events. Contemporary criteria of Adult Treatment Panel-III allow determining subjects with established obesity and various metabolic abnormalities, i.e. increased fasting glucose, impaired glucose tolerance dyslipidemia and insulin resistance (IR), are referred metabolically unhealthy obesity (Met-UHO), whereas individuals without these findings could be defined as those who have metabolically healthy obesity (Met-HO). The mechanisms underlying the change in phenotype from Met-HO to Met-UHO are yet not understood. It has been postulated that apoptotic endothelial cell-derived micro particles (EMPs) could be a trigger of endothelial cell dysfunction and as well as a mediator on vascular repair. Moreover, the imbalance in circulating number of various type of EMPs may influence the risk of transformation of Met-HO into Met-UHO. The short communication is depicted the role of apoptotic EMPs in obesity phenotype modification.

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“…As a derivate of cellular membrane MPs are discussed powerful paracrine regulators of target cell structure and functions. MP released by apoptotic endothelial cells posse a wide spectrum of biological effects on intercellular communication by transferring (Alexandru et al, 2016). Additionally, apoptotic endothelial cellderived MPs (EMPs) may directly worse endothelial integrity and vascular function playing a pivotal role in development of microvascular inflammation and IR (Alexandru et al, 2016;Berezin et al, 2016b).…”

Section: Introductionmentioning

confidence: 99%

Circulating apoptotic endothelial cell-derived microparticles are predicted metabolically unhealthy obesity

Berezin

Kremzer

Berezina³

et al. 2017

Biomed Res Ther

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Introduction: Circulating apoptotic endothelial cell-derived micro particles (EMPs) are a marker of endothelial dysfunction and cardiovascular (CV) risk in type 2 diabetes mellitus patients. There is evidence regarding association between apoptotic EMP number and CV disease in obese individuals. The aim of the study to investigate whether increased number of circulating apoptotic EMPs may predict transformation of Met-HO into Met-UHO. Methods: The study was retrospectively evolved 89 patients with established abdominal obesity (47 patients with Met-UHO determined as MetS and 42 subjects with Met-HO) from the large cohort of abdominal obesity patients (n=268). Thirty five healthy volunteers matched for age and sex were involved in the study as a control cohort. Obesity-related biomarker (adiponectin, leptin, vistafin) and EMPs were measured at baseline. Flow cytometry was used to determine EMPs with immune phenotype CD31+/ annexin V+ and CD144+/annexin V+. Results: There was not found a significant difference between numbers of EMPs labeled CD31 + / Annexin V + in Met-UHO and Met-HO patients, while Met-UHO patients had a significantly increased level of circulating CD144 + / Annexin V + compared with Met-HO individuals. Multivariate logistic regression analysis has revealed the HOMA-IR, number of CV risk factors, serum leptin and hs-CRP independently predicted numbers of circulating CD31 + / Annexin V + and CD144 + / Annexin V + EMPs in Met-UHO. In Met-HO patients HOMA-IR remained an independent predictor of increased numbers of circulating CD31 + / Annexin V + and CD144 + / Annexin V + EMPs. Conclusion: in the investigation we found that the increased number of CD31 + /Annexin V + and CD144 + / Annexin V + EMPs added to the based predictive model (HOMA-IR) may predict transformation of Met-HO into Met-UHO.

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Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players

Cited by 68 publications

References 131 publications

Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition

Blood Brain Barrier Injury in Diabetes: Unrecognized Effects on Brain and Cognition

Biosensing of Circulating Apoptotic Endothelial Cell Micro particles: The Impact in Risk Stratification of Obesity

Circulating apoptotic endothelial cell-derived microparticles are predicted metabolically unhealthy obesity

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