Vascular Senescence and Atherosclerotic Plaque Vulnerability

NCT06313645 | Recruiting

• 1 other identifier: B83C22004880006
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Chronological aging significantly contributes to structural and functional alterations in the vasculature, making it a major risk factor for atherosclerotic disease and its acute thrombotic events. DNA damage, including telomeric, non-telomeric, and mitochondrial damage, is recognized as a key initiator of vascular aging and atherogenesis. There is abundant evidence indicating the presence of oxidative DNA lesions, telomere erosion, and mitochondrial DNA damage in both experimental and human plaques, as well as in the peripheral cells of atherosclerotic patients. It is increasingly evident that genomic instability activates signaling pathways that lead to a multitude of pathophysiological cellular and molecular changes. These changes promote inflammation, apoptosis, autophagy, and ultimately, cellular senescence, accompanied by the "senescence-associated secretory phenotype" (SASP). However, the precise mechanisms linking the DNA damage response (DDR) to senescence, SASP in vascular cells, and the pathogenesis of atherosclerosis and vulnerable atheroma are yet to be fully understood. Additional research is needed to delineate the underlying mechanisms through which mitochondrial dysfunction influences telomere length and vice versa, and how their interaction contributes to the vascular aging process. Progress in this area has the potential to uncover therapeutic targets and novel, more precise diagnostic, and prognostic indicators. The objectives of the VICTORIA study are to examine the levels of aging-related non-coding RNA deregulation (specifically lncRNA TERRA and mitomiR) and peripheral markers of cell aging (including telomere length and mitochondrial DNA content) across the various spectra of angina pectoris (stable angina, unstable angina, NSTEMI, and STEMI). Additionally, the study aims to determine whether these markers are correlated with vulnerable plaque characteristics and major adverse cardiovascular events.

Conditions

Coronary Artery Disease

Keywords

Vascular senescence; Genetic instability; Mitochondrial deregulation; Coronary syndrome

Outcome Measures

Primary Outcomes (1)

• Telomere length

  Telomere length (LTL) is an index of genetic instability and senescence. LTL is measured in the DNA (extracted from blood leucocytes) by RT-PCR. Measure unit: 2\^(-ddct) or kilobases

  T0, at the enrollment

Secondary Outcomes (4)

• Mitochondrial DNA copy number (mtDNAcn)

  T0, at the enrollment

• MitomiR

  T0, at the enrollment

• Long non-coding (lnc) RNA TERRA

  T0, at the enrollment

• pro-oxidant cytokines

  T0, at the enrollment

Study Arms (1)

Patients with coronary artery diseases

Patients with acute coronary syndromes \[unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI)\] and with stable angina or non-angiographically coronary diseases recovered for elective diagnostic or interventional procedures are included in the study

Other: Several biomarkers

Interventions

Several biomarkers OTHER

Telomere length Mitochondrial DNA copy number (mtDNAcn) MitomiR long non-coding (lnc) RNA TERRA pro-oxidant cytokines \& chemokines

Patients with coronary artery diseases

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with acute or chronic coronary syndromes

You may qualify if:

• Patients with acute coronary syndromes (unstable angina, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI))
• stable angina
• non-angiographically significant coronary diseases recovered for elective diagnostic or interventional procedures

You may not qualify if:

• cardiac shock
• congestive heart failure
• end stage renal diseases
• coronary artery bypass graft
• active cancer

Sponsors & Collaborators

• Niguarda Hospital: lead
• Istituto di Fisiologia Clinica CNR: collaborator

Study Sites (1)

ASST GOM Niguarda

Milan, Lombardy, 20162, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Samples with DNA- The following specimens were collected and stored at -80°C: whole blood, plasma, serum, clot, peripheral blood mononuclear cells (PBMCs)

MeSH Terms

Conditions

Coronary Artery Disease; Angina, Unstable

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Angina Pectoris; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Maria Grazia Andreassi, PhD

  IFC CNR Pisa

  STUDY DIRECTOR

Central Study Contacts

Jonica Campolo, MSc

CONTACT

+39026444; jonica.campolo@ospedaleniguarda.it

Emanuela Piccaluga, MD

CONTACT

+39026444; emanuela.piccaluga@ospedaleniguarda.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: March 15, 2024
• Study Start: July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

IT (1)