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Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions
Chiara Buono, … , Marcelo Amar, Howard S. Kruth
Chiara Buono, … , Marcelo Amar, Howard S. Kruth
Published April 13, 2009
Citation Information: J Clin Invest. 2009;119(5):1373-1381. https://doi.org/10.1172/JCI35548.
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Technical Advance Cardiology

Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions

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Abstract

The uptake of lipoproteins by macrophages is a critical step in the development of atherosclerotic lesions. Cultured monocyte-derived macrophages take up large amounts of native LDL by receptor-independent fluid-phase pinocytosis, either constitutively or in response to specific activating stimuli, depending on the macrophage phenotype. We therefore sought to determine whether fluid-phase pinocytosis occurs in vivo in macrophages in atherosclerotic lesions. We demonstrated that fluorescent pegylated nanoparticles similar in size to LDL (specifically nontargeted Qtracker quantum dot and AngioSPARK nanoparticles) can serve as models of LDL uptake by fluid-phase pinocytosis in cultured human monocyte–derived macrophages and mouse bone marrow–derived macrophages. Using fluorescence microscopy, we showed that atherosclerosis-prone Apoe-knockout mice injected with these nanoparticles displayed massive accumulation of the nanoparticles within CD68+ macrophages, including lipid-containing foam cells, in atherosclerotic lesions in the aortic arch. Similar results were obtained when atherosclerotic mouse aortas were cultured with nanoparticles in vitro. These results show that macrophages within atherosclerotic lesions can take up LDL-sized nanoparticles by fluid-phase pinocytosis and indicate that fluid-phase pinocytosis of LDL is a mechanism for macrophage foam cell formation in vivo.

Authors

Chiara Buono, Joshua J. Anzinger, Marcelo Amar, Howard S. Kruth

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Figure 7

Accumulation of quantum dots in mouse aorta atherosclerotic lesions occurs in vivo and in vitro.

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Accumulation of quantum dots in mouse aorta atherosclerotic lesions occu...
(A–C) Merged images of quantum dot (green) and nucleus (blue) fluorescence in the intima. Some red autofluorescence is present in the images in A and B. (A) Quantum dots (2 nmol) were injected into an Apoe-knockout mouse. After 24 hours, the aorta was harvested and processed for fluorescence microscopy. An aortic arch tissue section is shown, revealing accumulation of quantum dots in atherosclerotic lesions, mostly within cells. (B and C) Aortic arches from Apoe-knockout mice were cultured 24 hours with (B) or without (control) (C) 0.8 μM quantum dots. The accumulation of quantum dots within cells of atherosclerotic lesions was similar to that observed in vivo. The lumen region is indicated. Scale bar: 2 μm.

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