Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

Westerweel, Peter E.; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E.; White, Ian; Hooper, Andrea T.; Doevendans, Pieter A.; Verhaar, Marianne C.

doi:10.1371/journal.pone.0060357

Cited by 63 publications

(51 citation statements)

References 56 publications

(82 reference statements)

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“…In addition to the altered cytokine gradient, decreased NO, increased reactive oxygen species, and advanced glycation end products in DM impair this migration. 39,50,52 These pathological processes induced by DM also increase apoptosis and decrease proliferation of EPCs. Both in vitro and in vivo studies have shown that hyperglycemia and its associated lipotoxicity with elevated oxidized low-density lipoprotein increases the senescence or apoptosis of EPCs mediated through multiple different molecular pathways, including interleukin 8, Akt, protein kinase C, and p38 mitogen-activated protein kinase ( Figure 1B).…”

Section: Trafficking and Survivalmentioning

confidence: 99%

“…[49][50][51][52][53] Although these abnormalities might not cause a major defect in hematopoiesis, they are associated with reduced differentiation and release of EPCs. Experimental 50,51 and human studies 54,55 also demonstrate that DM impairs the mobilization of EPCs in response to tissue ischemia or cytokines, such as granulocyte colony-stimulating factor.…”

Section: Differentiation and Mobilizationmentioning

confidence: 99%

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Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

Yiu

Tse

2014

ATVB

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Abstract-The disease burden of diabetes mellitus (DM) and its associated cardiovascular complications represent a growing and major global health problem. Recent studies suggest that circulating exogenous endothelial progenitor cells (EPCs) play an important role in endothelial repair and neovascularization at sites of injury or ischemia. 1 This has been attributed to the occurrence of endothelial dysfunction that leads to the initiation and progression of atherosclerotic vascular disease 2 and impaired neovascularization after ischemia induced by hyperglycemia. 3,4 In patients with impaired glucose metabolism and DM, the vascular endothelium is challenged by inflammation, reactive oxygen species, and deletion of endothelial nitric oxide synthase (eNOS) with resultant endothelial dysfunction.2,5-7 The depletion and dysfunction of the circulating endothelial progenitor cells (EPCs) are thought to underlie the endothelial dysfunction in DM. In this review, the possible mechanisms, functional consequences, and the potential therapeutic approach for impaired EPCs in DM are discussed. A systematic literature search for full-text papers in the English language was performed using MEDLINE, Embase, and the Cochrane library through to February 2014. In the search phrases used, the following terms were combined with the phrase AND Diabetes: endothelial progenitor cells, cardiovascular disease, myocardial infarction, and stroke.

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Section: Trafficking and Survivalmentioning

confidence: 99%

Section: Differentiation and Mobilizationmentioning

confidence: 99%

Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

Yiu

Tse

2014

ATVB

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“…Additionally, diabetes causes bone marrow microangiopathy and dysfunction in animal models (23), which is thought to play a role in low EPC number and mobilization in diabetic humans (2). In mouse models of diabetes, the mobilization of hematopoietic progenitor cells is impaired due to alterations in the bone marrow stroma (14,38), a finding that corresponds with impaired mobilization of hematopoietic progenitor cells in diabetic humans in response to granulocyte-colony stimulating factor administration (14). The exercise-induced release of EPC mobilizing factors and the "health" of bone marrow warrant further study to determine the causes of impaired EPC mobilization in IGT and T2DM.…”

Section: Discussionmentioning

confidence: 99%

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

et al. 2016

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Lutz AH, Blumenthal JB, Landers-Ramos RQ, Prior SJ. Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes. J Appl Physiol 121: 36 -41, 2016. First published May 19, 2016 doi:10.1152/japplphysiol.00349.2016.-Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM-associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 yr of age) men and women with NGT (n ϭ 18), IGT (n ϭ 10), or T2DM (n ϭ 17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2ϩ (VEGFR2ϩ) cells, CD34ϩ hematopoetic progenitor cells, and CD34ϩ/VEGFR2ϩ EPCs by flow cytometry before and after exercise. Basal EPC number was 65 and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P Ͻ 0.05). EPC number increased 23% after acute exercise in the NGT group (P Ͻ 0.01), but did not change in the IGT or T2DM groups. Before and after exercise, VEGFR2ϩ cell number was lower in a stepwise manner across the NGT, IGT, and T2DM groups (P Ͻ 0.05). Basal CD34ϩ cell number was lower in the IGT group compared with NGT (P Ͻ 0.05), but did not change after exercise in any group. These findings suggest a CD34ϩ/VEGFR2ϩ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance.

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“…• In rats, induction of mobilisation of stem cells from the BM to peripheral blood by ischaemia [112,125] and G-CSF [113,124] is impaired in type 1 diabetes.…”

Section: Features Of the Diabetic Bmmentioning

confidence: 99%

“…• In mice, type 1 diabetes alters BM niche function, gene expression and cytokine production [113,[122][123][124].…”

Section: Features Of the Diabetic Bmmentioning

confidence: 99%

A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications

Fadini

2013

Diabetologia

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Traditionally, the development of diabetic complications has been attributed to the biochemical pathways driving hyperglycaemic cell damage, while reparatory mechanisms have been long overlooked. A more comprehensive view of the balance between damage and repair suggests that an impaired regenerative capacity of bone marrow (BM)-derived cells strongly contributes to defective re-endothelisation and neoangiogenesis in diabetes. Although recent technological advances have redefined the biology and function of endothelial progenitor cells (EPCs), interest in BM-derived vasculotropic cells in the setting of diabetes and its complications remains high. Several circulating cell types of haematopoietic and non-haematopoietic origin are affected by diabetes and are potentially involved in the pathobiology of chronic complications. In addition to classical EPCs, these include circulating (pro-)angiogenic cells, polarised monocytes/macrophages (M1 and M2), myeloid calcifying cells and smooth muscle progenitor cells, having disparate roles in vascular biology. In parallel with the study of elusive progenitor cell phenotypes, it has been recognised that diabetes induces a profound remodelling of the BM stem cell niche. The alteration of circulating (progenitor) cells in the BM is now believed to be the link among distant end-organ complications. The field is rapidly evolving and interest is shifting from specific cell populations to the complex network of interactions that orchestrate trafficking of circulating vasculotropic cells.

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Impaired Endothelial Progenitor Cell Mobilization and Dysfunctional Bone Marrow Stroma in Diabetes Mellitus

Cited by 63 publications

References 56 publications

Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes

A reappraisal of the role of circulating (progenitor) cells in the pathobiology of diabetic complications

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