Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes

Chen, M.-C.; Sheu, Jiunn‐Jye; Wang, P.-W.; Chen, C.-Y.; Kuo, Mei‐Chuan; Hsieh, Chin-Ling; Chen, J.-F.; Chang, Hak

doi:10.1111/j.1464-5491.2008.02649.x

Cited by 24 publications

(13 citation statements)

References 29 publications

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“…Microvascular complications and subsequent critical limb ischemia were major health care concerns related to diabetes. However, vascular complications in diabetes led to reduced EPC numbers, angiogenicity, and other functions including migration (3,18). A progressive reduction of EPCs was further in parallel with increasing severity of peripheral vascular complications in those patients with type 2 diabetes (19).…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone Attenuates Endothelial Progenitor Cell Apoptosis Induced by TNF-α via ERK/MAPK and NF-κB Signal Pathways

Zhao

et al. 2011

J Pharmacol Sci

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Abstract. The discovery of endothelial progenitor cells (EPCs) provides us with a novel treatment strategy for complications requiring therapeutic revascularization and vascular repair. However, the feasibility of this strategy may be limited due to reduced number and impaired function of EPCs under stimulation of TNF-α. The present study was designed to investigate the effect of rosiglitazone on EPC apoptosis induced by TNF-α and the molecular mechanisms involved. Rosiglitazone attenuated apoptosis of TNF-α-stimulated EPCs in a dose-dependent manner. Rosiglitazone decreased caspase-3 activity and cleavages of caspase-3, caspase-7, and parp. Rosiglitazone also moderated the dissipation of mitochondrial membrane potential caused by TNF-α treatment and reduced the expression of bax and the release of cytochrome c. Furthermore, rosiglitazone inhibited phosphorylations of ERK/MAPK and NF-κB signal molecules. Both ERK and NF-κB inhibitors decreased TNF-α-induced apoptosis of EPCs, as well as the expression of cleaved caspase-3 and parp. These results suggest that rosiglitazone may mediate the inhibitory effect on EPCs apoptosis under TNF-α stimulation through suppression of ERK/MAPK and NF-κB signal pathways.

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Section: Discussionmentioning

confidence: 99%

Rosiglitazone Attenuates Endothelial Progenitor Cell Apoptosis Induced by TNF-α via ERK/MAPK and NF-κB Signal Pathways

Zhao

et al. 2011

J Pharmacol Sci

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“…Despite profound methodologic differences among studies, EPCs appear to be consistently reduced or impaired in the setting of virtually all risk factors for cardiovascular disease [38]. It is shown that the migratory function of EPCs is impaired in patients with T2DM, and EPCs are reduced in peripheral vascular complications of T2DM [39]. These findings presented an insight into the pathogenesis of impaired neovascularization and critical limb ischemia in diabetic patients.…”

Section: Methods For Ex Vivo Evaluation Of Human Vascular Endothelialmentioning

confidence: 99%

Human Vascular Endothelial Cells: A Model System for Studying Vascular Inflammation in Diabetes and Atherosclerosis

et al. 2011

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The vascular endothelium is the inner lining of blood vessels serving as autocrine and paracrine organ that regulates vascular wall function. Endothelial dysfunction is recognized as initial step in the atherosclerotic process and is well advanced in diabetes, even before the manifestation of end-organ damage. Strategies capable of assessing changes in vascular endothelium at the preclinical stage hold potential to refine cardiovascular risk. In vitro cell culture is useful in understanding the interaction of endothelial cells with various mediators; however, it is often criticized due to the uncertain relevance of results to humans. Although circulating endothelial cells, endothelial microparticles, and progenitor cells opened the way for ex vivo studies, a recently described method for obtaining primary endothelial cells through endovascular biopsy allows direct characterization of endothelial phenotype in humans. In this article, we appraise the use of endothelial cell-based methodologies to study vascular inflammation in diabetes and atherosclerosis.

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“…A negative correlation between CPC number and cardiovascular complications was found in Type 2 diabetes [8], [9]. Other studies suggest that the viability and migration capacity of CPCs are impaired in diabetic patients, whereas CPC counts are not dramatically altered [10], [11], [12]. Furthermore, the usefulness of CPCs for cardiovascular risk stratification in diabetic versus non-diabetic patients remains undefined.…”

Section: Introductionmentioning

confidence: 98%

Stepwise Optimization of the Procedure for Assessment of Circulating Progenitor Cells in Patients with Myocardial Infarction

et al. 2012

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BackgroundThe number and functional activity of circulating progenitor cells (CPCs) is altered in diabetic patients. Furthermore, reduced CPC count has been shown to independently predict cardiovascular events. Validation of CPCs as a biomarker for cardiovascular risk stratification requires rigorous methodology. Before a standard operation protocol (SOP) can be designed for such a trial, a variety of technical issues have to be addressed fundamentally, which include the appropriate type of red blood cell lysis buffer, FMO or isotype controls to identify rare cell populations from background noise, optimal antibody dilutions and conditions of sample storage. We herein propose improvements in critical steps of CPC isolation, antigenic characterization and determination of functional competence for final application in a prospective investigation of CPCs as a biomarker of outcome following acute myocardial infarction.Methods and FindingsIn this validation study, we refined the standard operating procedure (SOP) for flow cytometry characterisation and functional analysis of CPCs from the first 18 patients of the Progenitor Cell Response after Myocardial Infarction Study (ProMIS). ProMIS aims to verify the prognostic value of CPCs in patients with either ST elevation or non-ST elevation myocardial infarction with or without diabetes mellitus, using cardiac magnetic resonance imaging (MRI) for assessment of ventricular function as a primary endpoint. Results indicate crucial steps for SOP implementation, namely timely cell isolation after sampling, use of appropriate lysis buffer to separate blood cell types and minimize the acquisition events during flow cytometry, adoption of proper fluorophore combination and antibody titration for multiple antigenic detection and introduction of counting beads for precise quantification of functional CPC activity in migration assay.Conclusion and SignificanceWith systematic specification of factors influencing the enumeration of CPC by flow cytometry, the abundance and migration capacity of CPCs can be correctly assessed. Adoption of validated SOP is essential for refined comparison of patients with different comorbidities in the analysis of risk stratification.

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Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes

Cited by 24 publications

References 29 publications

Rosiglitazone Attenuates Endothelial Progenitor Cell Apoptosis Induced by TNF-α via ERK/MAPK and NF-κB Signal Pathways

Rosiglitazone Attenuates Endothelial Progenitor Cell Apoptosis Induced by TNF-α via ERK/MAPK and NF-κB Signal Pathways

Human Vascular Endothelial Cells: A Model System for Studying Vascular Inflammation in Diabetes and Atherosclerosis

Stepwise Optimization of the Procedure for Assessment of Circulating Progenitor Cells in Patients with Myocardial Infarction

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