Endothelial progenitor cells in atherosclerosis

Du, Fuyong

doi:10.2741/4055

Cited by 119 publications

(118 citation statements)

References 226 publications

(254 reference statements)

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“…Collectively, this suggests that SIRT6 is a negative regulator of vascular oxidative stress and inflammation. In addition, our observational results on the negative modulation of SIRT6 levels in EPCs from diabetic patients open a new scenario in the signaling pathways underlying the EPC functional impairment during atherosclerosis and diabetes (20,22). However, although our findings suggest that diabetes determines an increase of oxidative stress, NF-kB activation, and SIRT6 expression, the mechanism by which SIRT6 acts in the regulation of the type 2 diabetic plaque phenotype is unknown.…”

Section: Discussionmentioning

confidence: 48%

“…It is already known from experimental and clinical studies (22) that atherosclerosis is associated with a reduced number and dysfunction of EPCs. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we looked at the possible involvement of SIRT6 by evaluating its expression levels in EPCs isolated from the peripheral blood of 10 nondiabetic patients and 10 diabetic patients (5 current incretin users and 5 never incretin users).…”

Section: Sirt6 Protein Levels In Epcs From Diabetic and Nondiabetic Pmentioning

confidence: 99%

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Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment

et al. 2014

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The role of sirtuin 6 (SIRT6) in atherosclerotic progression of diabetic patients is unknown. We evaluated SIRT6 expression and the effect of incretin-based therapies in carotid plaques of asymptomatic diabetic and nondiabetic patients. Plaques were obtained from 52 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Twenty-two diabetic patients were treated with drugs that work on the incretin system, GLP-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors for 26 6 8 months before undergoing the endarterectomy. Compared with nondiabetic plaques, diabetic plaques had more inflammation and oxidative stress, along with a lesser SIRT6 expression and collagen content. Compared with non-GLP-1 therapy-treated plaques, GLP-1 therapy-treated plaques presented greater SIRT6 expression and collagen content, and less inflammation and oxidative stress, indicating a more stable plaque phenotype. These results were supported by in vitro observations on endothelial progenitor cells (EPCs) and endothelial cells (ECs). Indeed, both EPCs and ECs treated with high glucose (25 mmol/L) in the presence of GLP-1 (100 nmol/L liraglutide) presented a greater SIRT6 and lower nuclear factor-kB expression compared with cells treated only with high glucose. These findings establish the involvement of SIRT6 in the inflammatory pathways of diabetic atherosclerotic lesions and suggest its possible positive modulation by incretin, the effect of which is associated with morphological and compositional characteristics of a potential stable plaque phenotype.Cardiovascular disease represents the leading cause of death in patients with type 2 diabetes (1). Diabetes leads to increased vulnerability for plaque disruption, and mediates increased incidence and severity of clinical events (2). Inflammation, particularly in diabetes, plays a central role in the cascade of events that result in plaque erosion and fissuring (2). There is now increasing evidence that a number of transcription factors, including the Sir2 family of enzymes, namely sirtuins (SIRTs), regulate multiple genes whose products are putatively involved in the regulation of inflammation and endothelial cell (EC) function (3). The Sir2 family consists of seven enzymes (SIRT1 to SIRT7) that share a conserved core catalytic domain, but differ in their cellular localization and tissue distribution (4). Among the SIRTs, SIRT6, a chromatinassociated deacetylase, is considered to have a leading role in regulating genomic stability, cellular metabolism, stress response, and aging (5-8). A recent study (9) in mice suggested a role for SIRT6 in inflammation. Moreover, the knockdown of SIRT6 resulted in the increased expression of proinflammatory cytokines (interleukin [IL]-1b, IL-6, and IL-8), extracellular matrix remodeling enzymes (matrix metalloproteinase [MMP]-2, MMP-9, and plasminogen activator inhibitor 1), and intracellular adhesion molecule-1 (4). In ECs, the loss of SIRT6 was associated with an increased expression of nuclear factor-kB (NF-kB), whereas o...

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Section: Discussionmentioning

confidence: 48%

Section: Sirt6 Protein Levels In Epcs From Diabetic and Nondiabetic Pmentioning

confidence: 99%

Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment

et al. 2014

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“…These results support the hypothesis that ox-LDL is able to induce the apoptosis of HUVECs. This is significant since atherosclerosis has previously been associated with progressive endothelial cell loss (31). Therefore, the present study provides a potential mechanism by which ox-LDL exposure may enhance oxidative injury, in particular via induction of ROS production and activation of caspase-3.…”

Section: Discussionmentioning

confidence: 86%

Oxidized low-density lipoprotein decreases VEGFR2 expression in HUVECs and impairs angiogenesis

Zhang

2016

Experimental and Therapeutic Medicine

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Abstract. Atherosclerosis (AS), which is triggered by endothelial cell injury, evolves into a chronic inflammatory disease. Oxidized low-density lipoprotein (ox-LDL) is an important risk factor for the development of atherosclerosis; ox-LDL induces atherosclerotic plaque formation via scavenging receptors. The present study used ox-LDL-treated human umbilical vein endothelial cells (HUVECs) to investigate the effect of ox-LDL on angiogenesis. ox-LDL decreased HUVEC proliferation by MTT, induced apoptosis by Annexin V-fluorescein isothiocyanate (FITC) staining and markedly suppressed HUVEC tube formation by the Matrigel assay in a dose-dependent manner. Angiogenesis has been correlated with monocyte invasion, plaque instability and atherosclerotic lesion formation. In addition, ox-LDL induced the overproduction of reactive oxygen species using DCFH-DA staining and increased caspase-3 activity. Vascular endothelial growth factor receptor 2 (VEGFR2) were detected by quantitative polymerase chain reaction and western blot analysis and has previously been observed to have a key role in angiogenesis. Furthermore, the present study demonstrated that the abundance of VEGFR2 was decreased in ox-LDL-treated HUVECs. These results suggested that ox-LDL impairs angiogenesis via VEGFR2 degradation, thus suggesting that VEGFR2 may be involved in adaptation to oxidative stress and AS.

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“…Clinical studies documented a decreased number of circulating EPCs in coronary artery disease (CAD) patients, suggesting that levels of circulating EPCs might be associated with vascular endothelial function and cardiovascular risk factors [17][18][19][20][21] . Hill et al [10] measured colony-forming units of EPCs from patients with different degrees of cardiovascular risk but without history of cardiovascular disease.…”

Section: Epc Number and Function In Cardiovascular Diseasesmentioning

confidence: 99%

“…It was also found that EPCs from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk. Subsequently, it was demonstrated that reduced level of circulating EPCs independently predicts atherosclerotic disease progression and development of cardiovascular events [17][18][19] . Sen et al [17] , suggested that EPC determines the quality of the coronary collateral circulation.…”

Section: Epc Number and Function In Cardiovascular Diseasesmentioning

confidence: 99%

Enhancing endothelial progenitor cell for clinical use

Poh

2015

WJSC

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Circulating endothelial progenitor cells (EPCs) have been demonstrated to correlate negatively with vascular endothelial dysfunction and cardiovascular risk factors. However, translation of basic research into the clinical practice has been limited by the lack of unambiguous and consistent definitions of EPCs and reduced EPC cell number and function in subjects requiring them for clinical use. This article critically reviews the definition of EPCs based on commonly used protocols, their value as a biomarker of cardiovascular risk factor in subjects with cardiovascular disease, and strategies to enhance EPCs for treatment of ischemic diseases.

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Endothelial progenitor cells in atherosclerosis

Cited by 119 publications

References 226 publications

Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment

Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment

Oxidized low-density lipoprotein decreases VEGFR2 expression in HUVECs and impairs angiogenesis

Enhancing endothelial progenitor cell for clinical use

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