Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease

Yu, Mengxue; Xie, Ruiqin; Zhang, Yan; Liang, Hui; Hou, Li; Yu, Chengyuan; Zhang, Jinming; Dong, Zengxiang; Tian, Ye; Bi, Yang; Kou, Junjie; Novakovic, Valerie A.; Shi, Jialan

doi:10.1093/ndt/gfy027

Cited by 24 publications

(23 citation statements)

References 49 publications

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“…Uremic toxins constitute the central one. To support, the PS + EV levels in vivo are inversely correlated with the glomerular filtration rate (Almquist et al, 2016;Yu et al, 2018), but positively with uric acid and proteinuria levels (Yu et al, 2018). More procoagulant MVs are detected in diabetes mellitus patients with CKD compared to patients without it (Almquist et al, 2016), and in patients with extreme albuminuria than in those with lower or normal levels (Yu et al, 2018).…”

Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 91%

“…To support, the PS + EV levels in vivo are inversely correlated with the glomerular filtration rate (Almquist et al, 2016;Yu et al, 2018), but positively with uric acid and proteinuria levels (Yu et al, 2018). More procoagulant MVs are detected in diabetes mellitus patients with CKD compared to patients without it (Almquist et al, 2016), and in patients with extreme albuminuria than in those with lower or normal levels (Yu et al, 2018). To get a laboratory verification, incubation of normal endothelial cells or red blood cells (RBCs) with (i) patients' serum, (ii) uremic toxins at concentrations found in patients, or (iii) increased concentration of phosphate induce PS exposure on cells and EVs release (Faure et al, 2006;Abbasian et al, 2015;Gao et al, 2015a,b;Yu et al, 2018).…”

Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 99%

“…Endothelium and blood cells in CKD are characterized by increased rate of extracellular vesiculation. Significant proportion of EVs (in most studies, MVs) that are released following activation of the origin cells (Antonelou et al, 2011) expose phosphatidylserine (PS; Faure et al, 2006;Burton et al, 2013;Yu et al, 2018) and are prothrombotic, often more than the parent cells (Sinauridze et al, 2007), according to both morphological and biochemical evidence (Gao et al, 2015b;Yu et al, 2018). The intriguing finding that the platelet-derived MVs are less procoagulant than in other diseases (Trappenburg et al, 2012) (probably due to functional defects in platelets) does not break up the intimate relation of EVs with thrombosis in CKD, as uremic patients with thrombotic events have more MVs compared to those without events (Ando et al, 2002).…”

Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 99%

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The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients

Georgatzakou

Pavlou

Papageorgiou

et al. 2020

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) are membrane-enclosed nanoparticles released by most cells in body fluids and extracellular matrix. They function as signal transducers in intercellular communication, contributing to the maintenance of cell and tissue integrity. EVs biogenesis is deregulated in various pathologies, in structural and functional connection to the pathophysiology of donor cells. Consequently, EVs are considered diagnostic and monitoring factors in many diseases. Despite consensus as to their activity in promoting coagulation and inflammation, there is evidence suggesting protective roles for EVs in stress states. Chronic kidney disease (CKD) patients are at high risk of developing cardiovascular defects. The pathophysiology, comorbidities, and treatment of CKD may individually and in synergy affect extracellular vesiculation in the kidney, endothelium, and blood cells. Oxidative and mechanical stresses, chronic inflammation, and deregulation of calcium and phosphate homeostasis are established stressors of EV release. EVs may affect the clinical severity of CKD by transferring biological response modifiers between renal, vascular, blood, and inflammatory cells. In this Review, we focus on EVs circulating in the plasma of CKD patients. We highlight some recent advances in the understanding of their biogenesis, the effects of dialysis, and pharmacological treatments on them and their potential impact on thrombosis and vascular defects. The strong interest of the scientific community to this exciting field of research may reveal hidden pieces in the pathophysiology of CKD and thus, innovative ways to treat it. Overcoming gaps in EV biology and technical difficulties related to their size and heterogeneity will define the success of the project.

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Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 91%

Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 99%

Section: Evs In the Plasma Of Ckd Patients: General Outline Of Our Knmentioning

confidence: 99%

See 1 more Smart Citation

The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients

Georgatzakou

Pavlou

Papageorgiou

et al. 2020

Front. Cell Dev. Biol.

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“…PtdSer has been detected in microparticles in blood that have been implicated in hypercoagulation in diabetic kidney disease (Yu et al, 2018), cancer (Lea et al, 2017; Liu et al, 2019; Zhao et al, 2016), and inflammation (Zhao et al, 2016). Whether PtdSer is also an integral component of lipoproteins in humans is not known.…”

Section: Discussionmentioning

confidence: 99%

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

West

Michaelson

Miles

et al. 2020

Lipids

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The phospholipid composition of lipoproteins is determined by the specificity of hepatic phospholipid biosynthesis. Plasma phospholipid 20:4n‐6 and 22:6n‐3 concentrations are higher in women than in men. We used this sex difference in a lipidomics analysis of the impact of endocrine factors on the phospholipid class and molecular species composition of fasting plasma from young men and women. Diester species predominated in all lipid classes measured. 20/54 Phosphatidylcholine (PtdCho) species were alkyl ester, 15/48 phosphatidylethanolamine (PtdEtn) species were alkyl ester, and 12/48 PtdEtn species were alkenyl ester. There were no significant differences between sexes in the proportions of alkyl PtdCho species. The proportion of alkyl ester PtdEtn species was greater in women than men, while the proportion of alkenyl ester PtdEtn species was greater in men than women. None of the phosphatidylinositol (PtdIns) or phosphatidylserine (PtdSer) molecular species contained ether‐linked fatty acids. The proportion of PtdCho16:0_22:6, and the proportions of PtdEtn O‐16:0_20:4 and PtdEtn O‐18:2_20:4 were greater in women than men. There were no sex differences in PtdIns and PtdSer molecular species compositions. These findings show that plasma phospholipids can be modified by sex. Such differences in lipoprotein phospholipid composition could contribute to sexual dimorphism in patterns of health and disease.

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“…circulating MPs are produced by a variety of cells, such as erythrocytes, granulocytes, monocytes, platelets, and endothelial cells (38). In recent years, studies have found that MPs induce hypercoagulability in a number of diseases, such as sepsis, stroke and nephrotic syndrome (39,40). The expression of phosphatidylserine (PS) is the underlying cause of MP-induced coagulation.…”

Section: Mps and Hypercoagulabilitymentioning

confidence: 99%

COVID‑19 and ischemic stroke: Mechanisms of hypercoagulability (Review)

Zhang

Wang

et al. 2021

Int J Mol Med

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During the coronavirus disease 2019 (COVID-19) pandemic, some patients with severe COVID-19 exhibited complications such as acute ischemic stroke (AIS), which was closely associated with a poor prognosis. These patients often had an abnormal coagulation, namely, elevated levels of D-dimer and fibrinogen, and a low platelet count. Certain studies have suggested that COVID-19 induces AIS by promoting hypercoagulability. Nevertheless, the exact mechanisms through which COVID-19 leads to a hypercoagulable state in infected patients remain unclear. Understanding the underlying mechanisms of hypercoagulability is of utmost importance for the effective treatment of these patients. The present review aims to summarize the current status of research on COVID-19, hypercoagulability and ischemic stroke. The present review also aimed to shed light into the underlying mechanisms through which COVID-19 induces hypercoagulability, and to provide therapies for different mechanisms for the more effective treatment of patients with COVID-19 with ischemic stroke and prevent AIS during the COVID-19 pandemic.

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Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease

Abstract: Our results suggest that PS+ MPs and MP-origin cells play procoagulant roles in patients with DKD. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients.

Cited by 24 publications

References 49 publications

The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients

The Multi-Faced Extracellular Vesicles in the Plasma of Chronic Kidney Disease Patients

Lipidomic Analysis of Plasma from Healthy Men and Women Shows Phospholipid Class and Molecular Species Differences between Sexes

COVID‑19 and ischemic stroke: Mechanisms of hypercoagulability (Review)

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