Abstract
BackgroundRupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI).MethodsAtherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured.ResultsDMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05).ConclusionAfter successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.
Highlights
Atherosclerosis (AS) is a pathological progression of chronic vascular inflammatory with a long time-course based on vascular lesions; it can cause severe complication such as myocardial infarction and stroke [1]
dimercaptosuccinic acid (DMSA)-ultra-small super paramagnetic iron oxide (USPIO) particles accumulated in vulnerable atherosclerotic plaques (VP) and rupture plaques
Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced magnetic resonance imaging (MRI), especially T2*-weighted sequences, with a signal strength peaking at 96 h
Summary
Atherosclerosis (AS) is a pathological progression of chronic vascular inflammatory with a long time-course based on vascular lesions; it can cause severe complication such as myocardial infarction and stroke [1]. Angiography is the most common technique used to assess cardiovascular risk by imaging arterial stenosis, but with the limitation that it cannot assess those lesions most prone to early rupture [3]; it provides little information on the composition of the atherosclerotic plaque. High-resolution intravascular imaging modalities, including intravascular ultrasound virtual histology and optical coherence tomography, permit direct imaging of the plaques and vessel wall [4]. These methods are invasive, expense and require expertise. And non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI)
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