Measurement of Aortic Cell Fluid-Phase Pinocytosis in vivo by Flow Cytometry

Anzinger, Joshua J.; Jin, Xueting; Palmer, Clovis S.; Dagur, Pradeep K.; Barthwal, Manoj Kumar; Kruth, Howard S.

doi:10.1159/000475934

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…To our knowledge, only two studies have investigated macrophage macropinocytosis in atherosclerotic arteries ( 46 , 47 ). These studies demonstrated that aortic macrophages internalize AngioSPARK fluorescent nanoparticles via macropinocytosis.…”

Section: Discussionmentioning

confidence: 99%

Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis

et al. 2022

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Accumulation of lipid-laden foam cells in the arterial wall plays a central role in atherosclerotic lesion development, plaque progression, and late-stage complications of atherosclerosis. However, there are still fundamental gaps in our knowledge of the underlying mechanisms leading to foam cell formation in atherosclerotic arteries. Here, we investigated the role of receptor-independent macropinocytosis in arterial lipid accumulation and pathogenesis of atherosclerosis. Genetic inhibition of fluid-phase macropinocytosis in myeloid cells ( LysMCre + Nhe1 fl/fl ) and repurposing of a Food and Drug Administration (FDA)–approved drug that inhibits macrophage macropinocytosis substantially decreased atherosclerotic lesion development in low-density lipoprotein (LDL) receptor–deficient and Apoe −/− mice. Stimulation of macropinocytosis using genetic ( H-RAS G12V ) and physiologically relevant approaches promoted internalization of unmodified native (nLDL) and modified [e.g., acetylated (ac) and oxidized (ox) LDL] lipoproteins in both wild-type and scavenger receptor (SR) knockout ( Cd36 −/− / Sra −/− ) macrophages. Pharmacological inhibition of macropinocytosis in hypercholesterolemic wild-type and Cd36 −/− / Sra −/− mice identified an important role of macropinocytosis in LDL uptake by lesional macrophages and development of atherosclerosis. Furthermore, serial section high-resolution imaging, LDL immunolabeling, and three-dimensional (3D) reconstruction of subendothelial foam cells provide visual evidence of lipid macropinocytosis in both human and murine atherosclerotic arteries. Our findings complement the SR paradigm of atherosclerosis and identify a therapeutic strategy to counter the development of atherosclerosis and cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis

et al. 2022

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“…Fluorescence nanoparticles and quantum dots of approximately similar size as of LDL were employed to investigate fluid phase pinocytosis in cultured macrophages. Both quantum dots and nanoparticles were taken up by macrophages in a linear fashion with no saturation effect that indicate no binding with receptor or carrier [26,27].…”

Section: Transportation Of Nanoparticles By Pinocytosismentioning

confidence: 99%

Transport Phenomenon of Nanoparticles in Animals and Humans

Ansari

2019

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Nanoparticles (NPs) are microscopic objects with at least one dimension less than 100 nm. These were first discovered by Michael Faraday in 1857 when he prepared gold nanoparticles and observed that nanostructured gold produced red color. This distinct feature of nanoparticles could be due to very small size. NPs are very small compared to the wavelengths of light, hence absorb light in the blue-green portion of the spectrum (~450 nm) and reflect the red light (~700 nm) thus yield a rich red color. NPs also possess very high surface to mass ratio that could be utilized in several application areas wherein a very high surface area is required. Nanoparticles witnessed tremendous growth in research and application areas especially in medicine in twentieth century after discovery of carbon nanotubes in 1991. Nanoparticles have been explored in medicine as targeted delivery carriers to deliver macromolecules such as proteins, enzymes, to the target organ up to cellular levels. Of late, these carriers have been employed to treat several tumors owing to its capacity to deliver chemotherapeutic agents to the tumor cells only thus improving efficacy and minimizing side effects of anticancer agents.

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“…Macrophages take up excessive amounts of LDL accumulated in the vascular wall via various mechanisms. Fluid-phase endocytosis of LDL, irrespective of its native or oxidized state, can be constitutive and receptor-independent [6] or activated by minimally oxidized LDL via TLR4/SYK signaling [7]. Macrophage uptake of oxidized LDL (OxLDL) is driven by OxLDL recognition by many pattern-recognition receptors, with CD36 and SR-A playing a major role [8].…”

Section: Macrophage Foam Cells and Nonfoamy Macrophagesmentioning

confidence: 99%

Macrophage inflammarafts in atherosclerosis

Li,

Navia-Pelaez,

Choi

et al. 2023

Current Opinion in Lipidology

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Purpose of review Advances in single cell techniques revealed a remarkable diversity in macrophage gene expression profiles in atherosclerosis. However, the diversity of functional processes at the macrophage plasma membrane remains less studied. This review summarizes recent advances in characterization of lipid rafts, where inflammatory receptors assemble, in macrophages that undergo reprogramming in atherosclerotic lesions and in vitro under conditions relevant to the development of atherosclerosis. Recent findings The term inflammarafts refers to enlarged lipid rafts with increased cholesterol content, hosting components of inflammatory receptor complexes assembled in close proximity, including TLR4-TLR4, TLR2-TLR1 and TLR2-CD36 dimers. Macrophages decorated with inflammarafts maintain chronic inflammatory gene expression and are primed to an augmented response to additional inflammatory stimuli. In mouse atherosclerotic lesions, inflammarafts are expressed primarily in nonfoamy macrophages and less in lipid-laden foam cells. This agrees with the reported suppression of inflammatory programs in foam cells. In contrast, nonfoamy macrophages expressing inflammarafts are the major inflammatory population in atherosclerotic lesions. Discussed are emerging reports that help understand formation and persistence of inflammarafts and the potential of inflammarafts as a novel therapeutic target. Summary Chronic maintenance of inflammarafts in nonfoamy macrophages serves as an effector mechanism of inflammatory macrophage reprogramming in atherosclerosis.

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Measurement of Aortic Cell Fluid-Phase Pinocytosis in vivo by Flow Cytometry

Cited by 7 publications

References 26 publications

Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis

Receptor-independent fluid-phase macropinocytosis promotes arterial foam cell formation and atherosclerosis

Transport Phenomenon of Nanoparticles in Animals and Humans

Macrophage inflammarafts in atherosclerosis

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