Influenza A VIRus and Destabilization of Atherosclerotic Carotid Plaques

NCT06217471 | Completed

• 1 other identifier: VIRAL V1 - 131/int/2019
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerosis is the main cause of cardiovascular diseases and is characterized by the accumulation of lipids and inflammatory cells such as macrophages and lymphocytes within the vessel wall of large and medium-sized arteries, forming so-called plaques. The underlying molecular mechanisms are not yet clearly understood. In particular, it is not yet clear what factors can cause the "destabilization" of atherosclerotic plaques, thus making them more vulnerable and prone to triggering acute cardiovascular events. Infectious agents have also been implicated in the pathogenesis of atherosclerosis. Some of them would be able to spread from the infected tissue and migrate to endothelial cells, promoting the secretion of inflammatory mediators and the oxidation of low-density lipoproteins (LDL), their accumulation in vascular cells and the formation of foam cells , fundamental mechanisms especially in the formation of vulnerable plaques. Recently, many studies have shown that the influenza virus can also play a role in the destabilization of atherosclerotic plaques. However, the role of influenza A virus (IVA) infection and related vaccination in the destabilization of atherosclerotic plaques is still controversial. Furthermore, the underlying molecular mechanisms are still a matter of investigation. Based on these data, we hypothesized that IV A infection may promote the destabilization of atherosclerotic plaques through a chronic postinfection immune response. This response would lead to systemic and local changes in the expression of pro-atherosclerotic cytokines and chemokines resulting in increased recruitment of monocyte macrophages and upregulation of the expression of scavenger receptors on the surface of macrophages with greater affinity for oxidized LDL (CD36 and Lectins- Like-oxLDL-receptor 1).

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (4)

• antigenic specificity of IV T cells

  To test the antigenic specificity of IV T cells in carotid plaques and blood samples (peripheral blood mononuclear immune cells - PBMCs) of patients undergoing carotid endarterectomy (CEA) using the Stimulation Index, comparing results among a group of patients with vulnerable carotid plaque (group A) and a group of patients with stable plaque (group B, controls). Collaterally, the presence of viral RNA in the carotid plaques of patients in both groups will be evaluated; Blood samples will also be evaluated with serology for the presence of antibodies against IV A.

  through study completion, an average of 3 years

• presence of viral RNA

  The presence of viral RNA in the carotid plaques and in the blood of patients in both groups will be evaluated using real-time PCR.

  through study completion, an average of 3 years

• expression of inflammatory chemokines/cytokines

  Evaluate and compare the expression of inflammatory chemokines/cytokines involved in the recruitment and differentiation of monocytes (especially IL-6, IL-1β, TNF-α, IFN-γ, MCP-1), in the carotid plaque and in the blood peripheral of both groups; the results will be correlated to those obtained in objective 1.

  through study completion, an average of 3 years

• expression of adhesion molecules and scavenger receptors

  To evaluate and compare the expression of adhesion molecules and scavenger receptors with high affinity for oxLDL (CD36 and lectin-like oxLDL receptor) in carotid plaques between the two groups. The results will be correlated to those obtained in objectives 1 and 2.

  through study completion, an average of 3 years

Interventions

Carotid Endoarterectomy PROCEDURE

Surgical removal of atherosclerotic plaque from the carotid artery, collection of blood samples

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients coming to the Vascular Surgery Unit of the IRCCS Policlinico San Donato to undergo carotid endarterectomy surgery for significant carotid stenosis

You may qualify if:

• adult patients (age \> 18 years) who have given their consent to participate in the study, belonging to the Vascular Surgery Unit of the IRCCS Policlinico San Donato to undergo carotid endarterectomy surgery for significant carotid stenosis (in accordance with the Guidelines International guidelines, asymptomatic patients with carotid stenosis \> 80% according to ECST and symptomatic patients with stenosis \> 70% according to ECST

You may not qualify if:

• Minor patients
• Pregnant/breastfeeding women
• Patients who have not provided their consent to participate in the study.

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead

Study Sites (1)

I.R.C.C.S. Policlinico San Donato

San Donato Milanese, Milan, 20097, Italy

Location

Related Publications (6)

• Madjid M, Naghavi M, Litovsky S, Casscells SW. Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies. Circulation. 2003 Dec 2;108(22):2730-6. doi: 10.1161/01.CIR.0000102380.47012.92. Epub 2003 Nov 10. No abstract available.

  PMID: 14610013 RESULT

• Chistiakov DA, Melnichenko AA, Myasoedova VA, Grechko AV, Orekhov AN. Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl). 2017 Nov;95(11):1153-1165. doi: 10.1007/s00109-017-1575-8. Epub 2017 Aug 7.

  PMID: 28785870 RESULT

• Guan X, Yang W, Sun X, Wang L, Ma B, Li H, Zhou J. Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction. Inflamm Res. 2012 Jun;61(6):591-8. doi: 10.1007/s00011-012-0449-3. Epub 2012 Feb 29.

  PMID: 22373653 RESULT

• Keller TT, van der Meer JJ, Teeling P, van der Sluijs K, Idu MM, Rimmelzwaan GF, Levi M, van der Wal AC, de Boer OJ. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques. Stroke. 2008 Jan;39(1):174-9. doi: 10.1161/STROKEAHA.107.491282. Epub 2007 Nov 29.

  PMID: 18048854 RESULT

• Haidari M, Wyde PR, Litovsky S, Vela D, Ali M, Casscells SW, Madjid M. Influenza virus directly infects, inflames, and resides in the arteries of atherosclerotic and normal mice. Atherosclerosis. 2010 Jan;208(1):90-6. doi: 10.1016/j.atherosclerosis.2009.07.028. Epub 2009 Jul 24.

  PMID: 19665123 RESULT

• Ricotta JJ, Aburahma A, Ascher E, Eskandari M, Faries P, Lal BK; Society for Vascular Surgery. Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease. J Vasc Surg. 2011 Sep;54(3):e1-31. doi: 10.1016/j.jvs.2011.07.031.

  PMID: 21889701 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

vascular atherosclerotic plaques, blood samples

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vascular Surgeon, Researcher, PI

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: January 22, 2024
• Study Start: February 18, 2020
• Primary Completion: March 9, 2023
• Study Completion: March 9, 2023
• Last Updated: January 22, 2024

Record last verified: 2024-01

Locations

IT (1)