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Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: To evaluate whether the direct renin inhibitor, aliskiren, has a more favorable effect compared to amlodipine on atherosclerotic biomarkers in patients with stable coronary artery disease and diabetes currently receiving standard secondary prevention therapy., Methods: A total of 38 patients were randomly assigned initially to either aliskiren (150 mg daily) or amlodipine (5 mg daily) for 2 weeks after which the dose of either medication was increased to its maximum daily dose for 4 additional weeks. Baseline and 6-week blood samples were analyzed for changes from baseline and between treatment groups for vascular and intracellular cell adhesion molecule, C-reactive protein, nitric oxide, plasminogen activator inhibitor 1, 8-isoprostane, and thiobarbituric acid reactive substances., Results: Thirty-one patients completed the study. More of the dropouts occurred in patients receiving aliskiren. Systolic blood pressure decreased in both treatment arms with no differences between the groups being noted. Plasminogen activator inhibitor 1, nitric oxide, and C-reactive protein concentrations increased in both groups from baseline but changes from baseline or between groups were not significant. Vascular and intracellular cell adhesion molecule, thiobarbituric acid reactive substances, and isoprostane concentrations decreased in each treatment arm from baseline, but these changes were not significant and no differences were noted between the groups., Conclusions: Treatment with either aliskiren or amlodipine did not significantly alter surrogate biomarkers of atherosclerosis in patients with both diabetes and established cardiovascular disease already receiving appropriate secondary cardiovascular prevention therapy. The study is limited in its size and duration to see an effect.