The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ACVD) since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. However, our recent results indicate that telomere length (TL) is mainly determined before adulthood, by TL at birth and TL attrition during growth. They also demonstrate that short telomeres precede the clinical manifestation of atherosclerosis. The investigators therefore hypothesize that LT is not a simple marker, but a major determinant of arterial aging.
Two mechanistic hypotheses may explain an active role of short telomeres in accelerated arterial aging and development of ACVD.
The first is that a short TL at the leukocyte level reflects a short TL in endothelial progenitor cells (EPC). Cell replicative capacity being TL-dependent, short telomeres in the EPC would therefore be responsible for diminished replication capacity and vascular repair potential, thereby increasing the vulnerability for developing age-related arterial diseases.
The second hypothesis is that a short LTL reflects short TL in arterial wall cells, leading to an increase in the number of senescent vascular cells. Senescent cells are known to alter their secretion pattern, a phenomenon called senescence-associated secretory phenotype (SASP), and thus contribute to tissue injury by promoting inflammation and tissue remodeling leading to lesion progression.
These assumptions cannot be tested by LTL measurements alone. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues and cell types: leukocytes, circulating EPCs, in situ EPCs and arterial resident cells (mainly smooth muscle cells) in patients with or without atherosclerosis.
Our model is based on the following observations:
The general aim of the present project is to examine the mechanistic links between arterial aging and TL in these different cell types.
Condition or disease |
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Atherosclerosis of Artery |
Study Type : | Observational [Patient Registry] |
Estimated Enrollment : | 100 participants |
Observational Model: | Case-Control |
Time Perspective: | Cross-Sectional |
Target Follow-Up Duration: | 1 Day |
Official Title: | Role of Telomere Length in Arterial Smooth Muscle Cells and Circulating/Tissue Endothelial Progenitors in the Development of Atherosclerotic Lesions: Set up of the Experimental Model |
Actual Study Start Date : | May 8, 2019 |
Estimated Primary Completion Date : | April 20, 2021 |
Estimated Study Completion Date : | October 20, 2021 |
Group/Cohort |
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Control Group
Patients with traumatic vascular injury, ultimately corresponding to control patients
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Atheroma Group
Patients will be included either in the atheromatous group (patients with atheromatous pathology) or in the control group (patients without atheromatous pathology), according to the clinical evaluation. In the atheromatous group, subjects must have a clinically significant atheromatous pathology. The investigator must specify the site (s) affected by the atheroma: carotid artery, coronary artery, aorta, renal artery, mesenteric artery or lower limb artery. |
Description and comparison of telomere lengths in circulating and tissue endothelial progenitors in patients with atheromatous pathology and those with traumatic vascular disease.
The telomere length in the different cell types (expressed in kb) will be measured by Southern blot after DNA extraction.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Recruitment is expected in patients undergoing surgery giving access to arterial surgical residues.
Recruiter Service: Vascular Surgery at Nancy-Brabois University Hospital (Prof. Serguei Malikov)
As part of the clinical care, the samples available according to the groups are as follows:
Inclusion Criteria:
Exclusion Criteria:
France | |
Centre Hospitalier Régional Universitaire de Nancy | |
Nancy, France, 54000 |
Tracking Information | |||||
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First Submitted Date | April 24, 2019 | ||||
First Posted Date | April 26, 2019 | ||||
Last Update Posted Date | April 15, 2021 | ||||
Actual Study Start Date | May 8, 2019 | ||||
Estimated Primary Completion Date | April 20, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
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Original Primary Outcome Measures | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures |
TL in EPC [ Time Frame: Inclusion visit ] Description and comparison of telomere lengths in circulating and tissue endothelial progenitors in patients with atheromatous pathology and those with traumatic vascular disease.
The telomere length in the different cell types (expressed in kb) will be measured by Southern blot after DNA extraction.
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Original Secondary Outcome Measures | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | PROGENitors, TELomeres and ARTerial Aging | ||||
Official Title | Role of Telomere Length in Arterial Smooth Muscle Cells and Circulating/Tissue Endothelial Progenitors in the Development of Atherosclerotic Lesions: Set up of the Experimental Model | ||||
Brief Summary |
The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ACVD) since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. However, our recent results indicate that telomere length (TL) is mainly determined before adulthood, by TL at birth and TL attrition during growth. They also demonstrate that short telomeres precede the clinical manifestation of atherosclerosis. The investigators therefore hypothesize that LT is not a simple marker, but a major determinant of arterial aging. Two mechanistic hypotheses may explain an active role of short telomeres in accelerated arterial aging and development of ACVD. The first is that a short TL at the leukocyte level reflects a short TL in endothelial progenitor cells (EPC). Cell replicative capacity being TL-dependent, short telomeres in the EPC would therefore be responsible for diminished replication capacity and vascular repair potential, thereby increasing the vulnerability for developing age-related arterial diseases. The second hypothesis is that a short LTL reflects short TL in arterial wall cells, leading to an increase in the number of senescent vascular cells. Senescent cells are known to alter their secretion pattern, a phenomenon called senescence-associated secretory phenotype (SASP), and thus contribute to tissue injury by promoting inflammation and tissue remodeling leading to lesion progression. These assumptions cannot be tested by LTL measurements alone. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues and cell types: leukocytes, circulating EPCs, in situ EPCs and arterial resident cells (mainly smooth muscle cells) in patients with or without atherosclerosis. Our model is based on the following observations:
The general aim of the present project is to examine the mechanistic links between arterial aging and TL in these different cell types. |
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Detailed Description | Not Provided | ||||
Study Type | Observational [Patient Registry] | ||||
Study Design | Observational Model: Case-Control Time Perspective: Cross-Sectional |
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Target Follow-Up Duration | 1 Day | ||||
Biospecimen | Not Provided | ||||
Sampling Method | Non-Probability Sample | ||||
Study Population |
Recruitment is expected in patients undergoing surgery giving access to arterial surgical residues. Recruiter Service: Vascular Surgery at Nancy-Brabois University Hospital (Prof. Serguei Malikov) As part of the clinical care, the samples available according to the groups are as follows:
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Condition | Atherosclerosis of Artery | ||||
Intervention | Not Provided | ||||
Study Groups/Cohorts |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Suspended | ||||
Estimated Enrollment |
100 | ||||
Original Estimated Enrollment | Same as current | ||||
Estimated Study Completion Date | October 20, 2021 | ||||
Estimated Primary Completion Date | April 20, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers | No | ||||
Contacts | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT03928769 | ||||
Other Study ID Numbers | 2019-A00143-54 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Responsible Party | Central Hospital, Nancy, France | ||||
Study Sponsor | Central Hospital, Nancy, France | ||||
Collaborators | Not Provided | ||||
Investigators | Not Provided | ||||
PRS Account | Central Hospital, Nancy, France | ||||
Verification Date | January 2021 |