Nanomedicine-based strategies for treatment of atherosclerosis

Schiener, Maximilian; Hossann, Martin; Viola, Joana R.; Ortega‐Gómez, Almudena; Weber, Christian; Lauber, Kirsten; Lindner, Lars H.; Soehnlein, Oliver

doi:10.1016/j.molmed.2013.12.001

Cited by 83 publications

(49 citation statements)

References 99 publications

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“…S2B). Because the aorta is the primary target tissue whereas the liver and spleen are clearance organs, we determined accumulation in the aorta relative to these two organs (21). Our measurements showed a 3.4-fold difference between the highest and lowest aorta-to-liver accumulation ratios (NP5 vs. NP12, P < 0.01, Fig.…”

Section: Nanoparticles' Physiochemical Properties Affect Their In Vivomentioning

confidence: 88%

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Tang

Baxter

Menon

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

124

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Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis. Using the apolipoprotein E-deficient (Apoe −/− ) mouse model of atherosclerosis, we quantitatively evaluated the library's immune cell specificity by combining immunological techniques and in vivo positron emission tomography imaging. Based on this screen, we formulated a liver X receptor agonist (GW3965) and abolished its liver toxicity while still preserving its therapeutic function. Screening the immune cell specificity of nanoparticles can be used to develop tailored therapies for atherosclerosis and other inflammatory diseases.nanomedicine | drug delivery | immunotherapy | molecular imaging | atherosclerosis

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Section: Nanoparticles' Physiochemical Properties Affect Their In Vivomentioning

confidence: 88%

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Tang

Baxter

Menon

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

104

124

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“…The inconsistency between animal studies and the human trial could be due to insufficient dose of L-PLP, or a short treatment duration in the human trial 157, 159, 160 . Additionally, their effects on host defense in acute inflammatory situations are yet to be investigated 161 .…”

Section: Lipid Lowering and Anti-inflammatory Therapymentioning

confidence: 99%

Detection and treatment of atherosclerosis using nanoparticles

Zhang

Dhanasekara

et al. 2016

WIREs Nanomed Nanobiotechnol

100

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Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they are differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely and effectively detect the lesions in the early stages, nor can they characterize the lesion feature such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects.

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“…Thus, delivery strategies with arterial tropism may be favorable for future translational approaches. 20,21 Beyond its ability to reduce myeloid cell adhesion, AnxA1 exerts several proresolving effects that may be beneficial during atheroprogression and plaque destabilization. In this context, AnxA1 was identified as a bridging molecule opsonizing apoptotic cells to mediate efferocytosis.…”

Section: Circulation Researchmentioning

confidence: 99%

Annexin A1 Counteracts Chemokine-Induced Arterial Myeloid Cell Recruitment

Drechsler¹,

Jong²,

Rossaint³

et al. 2015

Circulation Research

Self Cite

128

123

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Rationale: Chemokine-controlled arterial leukocyte recruitment is a crucial process in atherosclerosis. Formyl peptide receptor 2 (FPR2) is a chemoattractant receptor that recognizes proinflammatory and proresolving ligands. The contribution of FPR2 and its proresolving ligand annexin A1 to atherosclerotic lesion formation is largely undefined. Objective: Because of the ambivalence of FPR2 ligands, we here investigate the role of FPR2 and its resolving ligand annexin A1 in atherogenesis. Methods and Results: Deletion of FPR2 or its ligand annexin A1 enhances atherosclerotic lesion formation, arterial myeloid cell adhesion, and recruitment. Mechanistically, we identify annexin A1 as an endogenous inhibitor of integrin activation evoked by the chemokines CCL5, CCL2, and CXCL1. Specifically, the annexin A1 fragment Ac2-26 counteracts conformational activation and clustering of integrins on myeloid cells evoked by CCL5, CCL2, and CXCL1 through inhibiting activation of the small GTPase Rap1. In vivo administration of Ac2-26 largely diminishes arterial recruitment of myeloid cells in a FPR2-dependent fashion. This effect is also observed in the presence of selective antagonists to CCR5, CCR2, or CXCR2, whereas Ac2-26 was without effect when all 3 chemokine receptors were antagonized simultaneously. Finally, repeated treatment with Ac2-26 reduces atherosclerotic lesion sizes and lesional macrophage accumulation. Conclusions: Instructing the annexin A1-FPR2 axis harbors a novel approach to target arterial leukocyte recruitment. With the ability of Ac2-26 to counteract integrin activation exerted by various chemokines, delivery of Ac2-26 may be superior in inhibition of arterial leukocyte recruitment when compared with blocking individual chemokine receptors.

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Nanomedicine-based strategies for treatment of atherosclerosis

Cited by 83 publications

References 99 publications

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Immune cell screening of a nanoparticle library improves atherosclerosis therapy

Detection and treatment of atherosclerosis using nanoparticles

Annexin A1 Counteracts Chemokine-Induced Arterial Myeloid Cell Recruitment

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