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Analysis of circulating microRNAs as potential non-invasive biomarkers of vulnerable plaque in patients with carotid stenosis for the prevention of atherothrombotic stroke.
The carotid artery is the main artery responsible for carrying blood to the neck. When an atheromatous plaque develops due to atherosclerosis, this plaque causes a decrease in the diameter of the arterial lumen, producing what is known as carotid stenosis. This stenosis is responsible for approximately 20-30% of ischaemic strokes due to "vulnerable plaques" that become trapped and generate a clot that occludes a distal cerebral artery. Although surgical intervention (endarterectomy) is considered the most effective option in patients who have developed symptoms, it is not as evident in asymptomatic patients. In patients with asymptomatic stenosis, plaque removal by endarterectomy can prevent stroke, but this surgical procedure carries risks that require proper patient selection. Unfortunately, (1) the classification of asymptomatic patients with vulnerable plaque (high risk of stroke) or with stable plaques (low risk of stroke) is difficult with the techniques currently used and (2) so far no non-invasive biomarkers predictive of vulnerable atheromatous plaque have been identified in patients with carotid stenosis. Currently, the characteristics of stenosis and the atheroma plaque that conditions it are only known after clinical follow-up of asymptomatic patients and analysis of the endarterectomy specimen, sometimes subjecting the patient to unnecessary surgery. There is, therefore, a need for biomarkers that, when stenosis is detected, allow us to discriminate between high-risk asymptomatic patients and stable asymptomatic patients in order to correctly select those patients at risk who can benefit from surgery.
The aim of the project is to identify microRNAs (miRNAs) as circulating biomarkers predictive of vulnerable plaque from their analysis in plasma samples of different types of patients with carotid stenosis >70% undergoing surgery (endarterectomy) in which the clinical course and the analysis of the plaques obtained in surgery has allowed them to be classified as symptomatic, risk asymptomatic and stable asymptomatic. The miRNAs identified in the different subgroups could be applied in daily clinical practice to identify the individual risk of each patient and decide the best therapeutic option.
The identification of miRNA biomarkers of vulnerable plaque, with a high risk of progression and rupture, complements the diagnostic and therapeutic decision tree used in daily clinical practice by vascular neurologists. This would detect subgroups of high-risk patients for whom surgical treatment is not currently indicated and, vice versa, would identify low-risk patients for whom medical treatment would be the best therapeutic option, avoiding the iatrogenesis associated with surgery.