Role of Influenza A VIRus in the Biomolecular Pathogenesis of the Destabilization of Atherosclerotic Carotid Plaques
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- presence of viral RNA
研究概览
简要总结
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).
详细描述
The following data will be collected anonymously from the medical records:
- personal details (age, sex);
- comorbidity (presence of cardiovascular risk factors: arterial hypertension, smoking, dyslipidemia, ischemic heart disease, COPD, diabetes mellitus; chronic renal failure, history of cerebrovascular ischemic events);
- history of flu vaccination;
- clinical (weight, height); As per clinical practice, patients will undergo carotid endarterectomy surgery. Upon entry into the operating room, patients will be taken 4 ml of blood in 4 tubes with a specific anticoagulant (EDTA), from a peripheral venous access already positioned for the surgical procedure regardless of the study. These blood samples will be stored and processed appropriately for individual analyses.
Samples of atherosclerotic plaque removed during surgery will also be stored appropriately for subsequent investigations.
The data collected will be entered into the dedicated e-CRF and appropriately analyzed.
Use of blood samples Peripheral blood mononuclear cells (PBMC) will be separated and isolated from the venous blood sample using a Percoll gradient. These cells will be appropriately stimulated with influenza A virus antigens using specific commercial kits. This process will allow the evaluation of immune reactivity to the virus, both in the group of patients with vulnerable carotid plaque (group A) and in those with non-vulnerable plaque (group B). On the serum of the same samples, the quantitative expression of some cytokines/chemokines involved in inflammation and the atherosclerotic process (IL-6, IL-1β, TNF-α, IFN-γ, MCP-1) will be evaluated using the ELISA method).
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Minor patients
- •Pregnant/breastfeeding women
- •Patients who have not provided their consent to participate in the study.
结局指标
主要结局
presence of viral RNA
时间窗: through study completion, an average of 3 years
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.
antigenic specificity of IV T cells
时间窗: through study completion, an average of 3 years
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.
expression of inflammatory chemokines/cytokines
时间窗: through study completion, an average of 3 years
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.
expression of adhesion molecules and scavenger receptors
时间窗: through study completion, an average of 3 years
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.
次要结局
未报告次要终点
研究者
Daniela Mazzaccaro
Vascular Surgeon, Researcher, PI
IRCCS Policlinico S. Donato