Abstract
Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.
Highlights
Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke
Human CEA specimens were collected from patients who presented to the Alfred Hospital, Melbourne, Australia with clinical indications for CEA
26 samples were from patients who presented with symptoms such as stroke or transient ischemic attacks, while 24 samples were from asymptomatic patients
Summary
Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. We have previously developed a mouse model that exhibits unstable plaques as seen in humans[16] This mouse model was instrumental for the description of NIRAF as a potential indicator of an atherosclerotic plaque’s risk in causing future cardiovascular events. Besides establishing fluorescence emission tomography (FLECT) as a preclinical tool for the detection of plaques with intraplaque hemorrhage and its potential use in testing and monitoring of plaque-stabilizing drugs, our report has the potential to support technical developments for imaging technologies that will allow to risk stratify atherosclerotic plaques in patients and, in particular, to identify plaques that are prone to cause cardiovascular events
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