Background: Atherosclerosis is a systemic inflammatory disease characterized by the formation of atheromatous plaques within arteries. These plaques can be classified as unstable or stable based on their morphology and cellular infiltrate. Anatomical location of plaques and age of atheroma defines the symptoms of disease. However, there is little in the literature to support this. The study aimed to compare the cellular composition, morphology, lipid biochemistry and 18F- flurodeoxyglucose (18F-FDG) positive emission tomography (PET) uptake between plaques from patients with recently symptomatic carotid disease and patients with symptomatic peripheral arterial disease undergoing intervention. Patients and Method Patients with symptomatic carotid (≥60%) or femoral stenosis undergoing intervention were recruited. All patients underwent 18F-FDG PET scanning prior to operation. The numbers of plaque macrophage and T cells were determined by immunohistochemistry (IHC). Double IHC defined the proportion of classically (M1) activated macrophages (iNOS, MHC II and SOCS-3 positive) or alternatively (M2) activated (dectin-1, CD163; SOCS-1). Plaque composition was quantified by a new morphological definition based on percentage area of fibrooconnective tissue, lipid, calcification and cellular infiltrate. The proportion of fatty acids within plaque lipids was estimated by liquid chromatography. Results 34 patients with symptomatic carotid disease and 34 with symptomatic femoral disease were recruited. 18F-FDG PET imaging was carried out successfully in 29 carotid and 29 femoral artery disease patients. 32 carotid and 25 femoral plaques were obtained. Significant differences were noted between carotid and femoral plaques with respect to the number of macrophages (p<0.001), T cells (p<0.001) and proportion of classical (p<0.001) and alternatively (p<0.001) activated macrophages and morphological analysis with evidence of more inflammation in carotid plaques. Lipid analysis revealed higher triglyceride n-6 PUFAs in carotid compared to femoral plaques (p=0.01). FDG uptake between carotid and femoral plaques was not significantly different and did not correlate with immunohistochemical, plaque morphometry or lipid analysis parameters. FDG uptake correlated with degree of symptomatic carotid stenosis (Spearman‟s coefficient=0.482;p=0.008) and symptomatic ABPI (Spearman‟s coefficient=-0.414;p=0.025). FDG uptake was higher in the symptomatic carotid compared to the contralateral asymptomatic carotid (p=0.016). Conclusion This study has shown substantial difference between morphological and cellular compositions of carotid and femoral plaques. Carotid plaques from recently symptomatic patients exhibited significantly greater percentage areas of lipid deposition, lymphocytic and monocyte/macrophage infiltrate and reduced cap thickness, in line with their more vulnerable nature. Moreover, there were a greater proportion of classically activated macrophages that are associated with plaque vulnerability. In contrast, percentage areas of fibroconnective tissue were higher in the femoral plaques. 18F-FDG PET imaging, although capable of identifying plaque inflammation, may not be adequately sensitive to differentiate between vulnerable and stable complex plaques.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:553870 |
| Date | January 2011 |
| Creators | Shaikh, Shafaque |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=174678 |
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