Clinical trial NCT03928769: 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
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Atherosclerosis of Artery
Keywords: Telomere length
Endothelial progenitor cell
Smooth muscle cell
Senescence
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2019-04-26
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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:

* for the group suffering from atheromatous pathology: lesion (pathological zone) and lesion border (healthy zone)
* for the group with traumatic vascular injury: lesion (but non-atheromatous lesion, therefore considered as control) and lesion border.

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.


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

Primary outcomes:
measure: Circulating EPC levels
timeFrame: Inclusion visit
measure: Tissue EPC levels
timeFrame: Inclusion visit
Secondary outcomes:
measure: TL in EPC
timeFrame: Inclusion visit
Other outcomes:
Locations:
city: Nancy
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy
Study officials:
References: