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Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis.

ABSTRACT: Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experimental atherosclerosis. In this work, we synthesized monocyte-targeting iron oxide magnetic nanoparticles (MNPs), which were incorporated with the peptides derived from the chemokine receptor C-C chemokine receptor type 2 (CCR2)-binding motif of monocytes chemoattractant protein-1 (MCP-1) as a diagnostic tool for potential atherosclerosis. MCP-1-motif MNPs co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knockout mice (ApoE KO mice), the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through in vivo imaging system (IVIS) imaging and magnetic resonance imaging (MRI). We also performed Oil Red O staining and Prussian Blue staining to confirm the co-localization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

SUBMITTER: Kao CW

PROVIDER: S-EPMC6027309 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis.

Kao Chung-Wei CW Wu Po-Ting PT Liao Mei-Yi MY Chung I-Ju IJ Yang Kai-Chien KC Tseng Wen-Yih Isaac WI Yu Jiashing J

Pharmaceutics 20180524 2

Atherosclerosis is a multifactorial inflammatory disease that may progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques from generating, imaging early molecular markers and quantifying the extent of disease progression are desired. During inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth facto ...[more]

PMID: 29795012

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Project description:BackgroundMonocyte chemoattractant protein 1 (MCP-1), acting in concert with its receptor chemokine receptor 2 (CCR2), promotes recruitment of macrophages into atherosclerotic plaque. We examined whether single nucleotide polymorphism (SNP) variants in the MCP-1 or CCR2 genes independently or in combination are associated with carotid artery atherosclerosis in an African American population at increased risk of vascular disease.MethodsFour SNPs in MCP-1 and 1 in CCR2 were genotyped. Carotid artery duplex ultrasonography was used to identify the presence or absence of carotid plaque >1 mm. The study population included 325 apparently healthy 30- to 59-year-old black siblings of 185 probands with premature coronary artery disease (<60 years old). Associations between each independent SNP and the presence of carotid plaque were examined using multivariate logistic regression models adjusted for age, sex, educational level, diabetes, smoking, hypertension, obesity, low-density lipoprotein cholesterol and non-independence within families. Interactions between SNPs in the MCP-1 gene and the SNP in the CCR2 gene were examined by multivariate analysis.ResultsSiblings were 32% males, with a mean age of 46 +/- 7 years, and 77 (24%) demonstrated carotid plaque. In multivariate analyses, the CC genotype of MCP-1 SNP rs2857656 was independently associated with plaque (p = 0.05). Subjects who had both the MCP-1 CC genotype and were heterozygotic or homozygotic for the CCR2 V64I genotype (rs1799864; n = 12) had an even higher risk of carotid atherosclerosis (odds ratio 6.14, 95% confidence interval 1.82-20.73; p = 0.0037).ConclusionThe MCP-1 rs2857656 CC genotype is independently associated with carotid artery plaque in African American from families with premature coronary artery disease. The combination of the MCP-1 CC homozygous genotype and the homozygotic or heterozygote CCR2 V64I genotype is associated with a particularly high prevalence of carotid artery plaque.

Dataset Information

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis.

Publications

Magnetic Nanoparticles Conjugated with Peptides Derived from Monocyte Chemoattractant Protein-1 as a Tool for Targeting Atherosclerosis.

Similar Datasets

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