Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation.

Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.

Objective-The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis. Methods and Results-Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by Pϭ0.016) and (2) 18F-FDG uptake evaluated by PET (rϭ0.5, Pϭ0.103 after clustered robust, Huber-White, standard errors analysis). Key Words: atherosclerosis Ⅲ inflammation Ⅲ neovessels Ⅲ MRI Ⅲ PET N eovascularization is one of the hallmarks of high-risk/ vulnerable atherosclerotic lesions. It is characterized by the formation of new capillaries in the atherosclerotic plaque, and it is usually considered a response to the hypoxic conditions within the vessel wall during plaque growth. 1 However, more recent reports have identified hypoxia independent pathways of angiogenesis mediated primarily by inflammation 2,3 : these studies have highlighted the link between the presence of neovessels, the extravasation and activation of inflammatory cells, and lipid deposition in the vessel wall. Neovessels seem to play a key role in the progression of atherosclerotic plaques and plaque rupture. 1 From those reports it appears that the presence and extent of neovessels and inflammation in atherosclerotic plaques can be considered a marker of risk associated with the lesion. Therefore it would be of clinical relevance to develop techniques capable of quantifying the degree of plaque inflammation in a noninvasive and reliable manner. DCE-MRI is an imaging technique extensively used to study the vascularity of tumors. 4 This technique takes advantage of the administration of clinically-available contrast agents (ie, Gadolinium (Gd)-chelates) to quantify the extent of tumor blood supply and its associated physiological characteristics, such as permeability surface area product, extraction fraction, and blood flow. Recent studies on human carotid atherosclerotic plaques have shown that several gadolinium uptake parameters, evaluated by kinetic modeling 5 of DCE-MRI bright blood acquisitions, correlate with the extent of plaque vascularity and macrophage burden (confirmed by staining of histological specimens). 6,7 However, the use of the bright blood DCE technique makes it intrinsically difficult to reliably delineate the vessel lumen from the w...

Macrophages play a key role in atherosclerotic plaque rupture. The iodine-based contrast agent N1177 accumulates in macrophages, allowing for their detection with CT. In this study, we tested whether the intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlated with inflammatory activity evaluated with 18 F-FDG PET/CT and macrophage density on histology. Methods: Atherosclerotic plaques were induced in the aorta of New Zealand White rabbits (n 5 7) by a repeated balloon injury (4 wk apart) and 4 mo of hyperlipemic diet. Noninjured rabbits, fed a chow diet, were used as controls (n 5 3). A CT scan of the aorta (n 5 10) was acquired in each rabbit before, during, and at 2 h after intravenous injection of N1177 (250 mg of iodine/kg). One week later, the same rabbits underwent PET/CT 3 h after injection of 18 F-FDG (37 MBq/kg [1 mCi/kg]). CT enhancement was calculated as the difference in aortic wall densities between images obtained before and images obtained at 2 h after injection of N1177. Mean standardized uptake values were measured on PET axial slices of the aorta in regions of interest encompassing the vessel wall. Macrophage density was measured by immunohistology (anti-RAM-11 antibody) on corresponding aortic cross-sections. Results: N1177-enhanced CT measured stronger enhancement in the aortic wall of atherosclerotic rabbits than in control rabbits (10.0 6 5.2 vs. 2.0 6 2.1 Hounsfield units, respectively; P , 0.05). After the injection of 18 F-FDG, PET detected higher standardized uptake values in the aortic wall of atherosclerotic rabbits than in control rabbits (0.61 6 0.12 vs. 0.21 6 0.02; P , 0.05). The intensity of enhancement in the aortic wall measured with CT after injection of N1177 correlated with 18 F-FDG uptake on PET/CT (r 5 0.61, P , 0.001) and macrophage density on immunohistology (r 5 0.63, P , 0.001). Conclusion: The intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlates with intense uptake of 18 F-FDG measured with PET and with macrophage density on histology, suggesting a role for N1177 in noninvasive identification of high-risk atherosclerotic plaques with CT.