Number and Replating Capacity of Endothelial Colony‐Forming Cells are Telomere Length Dependent: Implication for Human Atherogenesis

Toupance, Simon; Simonici, Stéphanie; Labat, Carlos; Dumoulin, Chloé; Lai, Tsung‐Po; Lakomy, Cécile; Régnault, V.; Lacolley, Patrick; Dignat-George, Françoise; Sabatier, Florence; Aviv, Abraham; Bénétos, Athanase; Gautier, Sylvie; Watfa, G.; Louis, Huguette; Folio, Mélanie; Schmitt, M; Ayad, Oualid; Didier, Agnès; Vauthier, Sandrine; François, Nelly; Visvikis‐Siest, Sophie; Stathopolou, Maria G.; Kimura, Masayuki; Rossi, P.; Béranger, Patricia; Malikov, Sergueï; Settembre, Nicla; Hubert, Jacques; Frimat, Luc; Bertrand, B.; Boufi, Mourad; Flecher, Xavier; Sadoul, Nicolas; Eschwège, P.; Kessler, Michèle; Tzanetakou, Irene P.; Doulamis, Ilias P.; Konstantopoulos, Panagiotis; Tzani, Aspasia; Korou, Marilina; Gkogkos, Anastasios; Menenakos, Evangelos; Samanidis, George; Vasiloglou‐Gkanis, Michail; Kark, Jeremy D.; Verhulst, Simon

doi:10.1161/jaha.120.020606

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…Atherosclerosis is an inflammatory process that develops in response to endothelial injury [35,36]. Multiple lines of evidence indicate that ECFCs play an important role in repairing injured vessels and in atherogenesis [8]. Conflicting data, however, exist regarding ECFC changes in PLHIV and their role in HIV-associated CVD development [37].…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial colony-forming cells (ECFCs), formerly known as late endothelial progenitor cells (EPCs), are derived from precursor cells that are activated upon vascular injury to promote angiogenesis, EC rejuvenation, and vascular repair [7]. There is evidence suggesting that early stages of atherogenesis are associated with decreased ECFC functionality and reduced ECFC counts [8]. Interestingly, it has been shown that PLHIV have decreased ECFC numbers and impaired ECFC functionality [9].…”

Section: Introductionmentioning

confidence: 99%

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HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs

Ferreira

Wei

Zhang

et al. 2023

IJMS

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People living with HIV (PLHIV) are at a higher risk of having cerebrocardiovascular diseases (CVD) compared to HIV negative (HIVneg) individuals. The mechanisms underlying this elevated risk remains elusive. We hypothesize that HIV infection results in modified microRNA (miR) content in plasma extracellular vesicles (EVs), which modulates the functionality of vascular repairing cells, i.e., endothelial colony-forming cells (ECFCs) in humans or lineage negative bone marrow cells (lin− BMCs) in mice, and vascular wall cells. PLHIV (N = 74) have increased atherosclerosis and fewer ECFCs than HIVneg individuals (N = 23). Plasma from PLHIV was fractionated into EVs (HIVposEVs) and plasma depleted of EVs (HIV PLdepEVs). HIVposEVs, but not HIV PLdepEVs or HIVnegEVs (EVs from HIVneg individuals), increased atherosclerosis in apoE−/− mice, which was accompanied by elevated senescence and impaired functionality of arterial cells and lin− BMCs. Small RNA-seq identified EV-miRs overrepresented in HIVposEVs, including let-7b-5p. MSC (mesenchymal stromal cell)-derived tailored EVs (TEVs) loaded with the antagomir for let-7b-5p (miRZip-let-7b) counteracted, while TEVs loaded with let-7b-5p recapitulated the effects of HIVposEVs in vivo. Lin− BMCs overexpressing Hmga2 (a let-7b-5p target gene) lacking the 3′UTR and as such is resistant to miR-mediated regulation showed protection against HIVposEVs-induced changes in lin− BMCs in vitro. Our data provide a mechanism to explain, at least in part, the increased CVD risk seen in PLHIV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs

Ferreira

Wei

Zhang

et al. 2023

IJMS

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“…ECFC senescence can be influenced by environmental systemic or local factors as well as by telomere integrity. Interestingly, we recently reported that formation and number of ECFC as well as their replating capacity are associated with telomere length [ 43 ]. ASCVD patients display shorter telomere length in leukocytes [ 44 ] and this telomere length is correlated with telomere length in ECFC [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we recently reported that formation and number of ECFC as well as their replating capacity are associated with telomere length [ 43 ]. ASCVD patients display shorter telomere length in leukocytes [ 44 ] and this telomere length is correlated with telomere length in ECFC [ 43 ]. Then, short telomere length in these cells could explain the observed senescence phenotype and reflect their diminished reparative capacity as previously observed in hematopoietic stem cells [ 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD)

Simoncini

Toupance

Labat

et al. 2022

IJMS

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Endothelial dysfunction is a key factor in atherosclerosis. However, the link between endothelial repair and severity of atherosclerotic cardiovascular disease (ASCVD) is unclear. This study investigates the relationship between ASCVD, markers of inflammation, and circulating endothelial progenitor cells, namely hematopoietic cells with paracrine angiogenic activity and endothelial colony forming cells (ECFC). Two hundred and forty-three subjects from the TELARTA study were classified according to the presence of clinical atherosclerotic disease. ASCVD severity was assessed by the number of involved vascular territories. Flow cytometry was used to numerate circulating progenitor cells (PC) expressing CD34 and those co-expressing CD45, CD34, and KDR. Peripheral blood mononuclear cells ex vivo culture methods were used to determine ECFC and Colony Forming Unit- endothelial cells (CFU-EC). The ECFC subpopulation was analyzed for proliferation, senescence, and vasculogenic properties. Plasma levels of IL-6 and VEGF-A were measured using Cytokine Array. Despite an increased number of circulating precursors in ASCVD patients, ASCVD impaired the colony forming capacity and the angiogenic properties of ECFC in a severity-dependent manner. Alteration of ECFC was associated with increased senescent phenotype and IL-6 levels. Our study demonstrates a decrease in ECFC repair capacity according to ASCVD severity in an inflammatory and senescence-associated secretory phenotype context.

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“…DNA quantity was assessed by spectrophotometry (Nanodrop, Thermo Fisher Scientific, Waltham, MA, USA). DNA samples passed integrity testing using a 1% (wt/vol) agarose gel prior to performing the TL measurement by Southern blot analysis of the terminal restriction fragments, as described previously [ 19 ]. Briefly, DNA samples were treated overnight with restriction enzymes HinfI and RsaI (Roche Diagnostics GmbH, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Association of Telomere Dynamics with Obesity and Metabolic Disorders in Young Children

et al. 2022

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In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders, such as obesity and diabetes mellitus type 2. These associations could stem from early life interactions between LTL and metabolic disorders. To test this hypothesis, we explored the associations between LTL and metabolic parameters as well as their evolution over time in children with or without obesity at baseline. Seventy-three (n = 73) children attending our Outpatient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, aged 2–10 years (mean ± SD: 7.6 ± 2.0 years), were followed for 2 to 4 years. Anthropometric, clinical, and biological (including LTL by Southern blot) measurements were performed annually. Baseline LTL correlated negatively with BMI (p = 0.02), fat percentage (p = 0.01), and blood glucose (p = 0.0007). These associations persisted after adjustments for age and sex. No associations were found between LTL attrition during the follow-up period and any of the metabolic parameters. In young children, obesity and metabolic disturbances were associated with shorter telomeres but were not associated with more pronounced LTL attrition. These results suggest that short telomeres contribute to the development of obesity and metabolic disorders very early in life, which can have a major impact on health.

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Number and Replating Capacity of Endothelial Colony‐Forming Cells are Telomere Length Dependent: Implication for Human Atherogenesis

Cited by 8 publications

References 37 publications

HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs

HIV Promotes Atherosclerosis via Circulating Extracellular Vesicle MicroRNAs

Functional Impairment of Endothelial Colony Forming Cells (ECFC) in Patients with Severe Atherosclerotic Cardiovascular Disease (ASCVD)

Longitudinal Association of Telomere Dynamics with Obesity and Metabolic Disorders in Young Children

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