PROGENitors, TELomeres and ARTerial Aging

NCT ID: NCT03928769

Last Updated: 2021-04-15

Basic Information

• Recruitment Status: SUSPENDED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-05-08
• Study Completion Date: 2021-10-20

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:

• TL is synchronized (equivalent) across somatic tissues/cells of the newborn: an individual with short telomeres (relative to his pairs) in one tissue should also have short telomeres (relative to his pairs) in other tissues.
• TL in EPCs (both circulating and in situ) determines the cell proliferative ability and therefore capacity for vessels repair during aging.
• TL in the cells of the arterial wall determines the number of senescent cells that therefore contribute to tissue injury through their change of phenotype.

The general aim of the present project is to examine the mechanistic links between arterial aging and TL in these different cell types.

Conditions

Atherosclerosis of Artery

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Control Group

Patients with traumatic vascular injury, ultimately corresponding to control patients

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Male or female ≥ 18 years
• Patient for whom a vascular surgery is programmed, and whose nature allows obtaining of arterial segment without any harm for the health of the patient
• Patient for whom a blood sample is planned on the day of the procedure
• Person who has received complete information on the organization of the research and who has not objected to his participation and the exploitation of his data
• Compulsory affiliation to social security

Exclusion Criteria

• Patient who has previously undergone radiotherapy at the sampling site
• Patient with cancer at the sampling site

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Centre Hospitalier Régional Universitaire de Nancy

Nancy, , France

Countries

France

Other Identifiers

2019-A00143-54

Identifier Type: -

Identifier Source: org_study_id