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  • 1
    Online Resource
    Online Resource
    Abstract 18687: PARP9 and PARP14 are Novel Regulators of Macrophage Activation
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Circulation Vol. 130, No. suppl_2 ( 2014-11-25)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 130, No. suppl_2 ( 2014-11-25)
    Abstract: Background: Pro-inflammatory “M1” macrophages may promote atherogenesis, while “M2” macrophages may favor an anti-inflammatory milieu. Our global proteomics of M1 and M2 cells identified ADP-ribosylation enzymes PARP9 and PARP14 as novel regulators of macrophage activation. The present study has examined the underlying mechanisms and explored in vivo evidence for their role in vascular disease. Methods and Results: IFN gamma (M1) stimulation induced and IL-4 (M2) decreased PARP9 and PARP14 in mouse and human macrophages. siRNA silencing of PARP14 enhanced expression of M1 genes (e.g. TNFα, iNOS) and activation (phosphorylation) of pro-inflammatory STAT1 while suppressing M2 markers (e.g., Arginase 1) and anti-inflammatory STAT6. Conversely, PARP9 silencing suppressed M1 polarization and STAT1 activation. These results suggest that PARP14 inhibits and PARP9 promotes a pro-inflammatory macrophage phenotype. Co-immunoprecipitation indicated that PARP14 and PARP9 physically interact. ADP-ribosylation assays revealed that PARP9 impairs PARP14-induced ribosylation (Figure A). Targeted proteomics via high-resolution mass spectrometry demonstrated that PARP14 ADP-ribosylates at least two sites in STAT1α, which PARP9 suppressed. Mechanically injured arteries of Parp14-/- mice had accelerated lesion formation and macrophage accumulation. Peritoneal and plaque macrophages of PARP14-/- mice showed increased STAT1 phosphorylation, decreased STAT6 phosphorylation, enhanced M1 gene expression, and reduced M2 responses (Figure B, laser capture microdissection). More macrophages[[Unable to Display Character: & #61472;]]were immunoreactive for PARP9 in human “unstable” plaques than in “stable” plaques (64.6±16.2% vs. 30.8±12.3%, p 〈 0.01, n=5). Conclusions: PARP14 and PARP9 reciprocally regulate the mechanisms of macrophage activation, offering the potential for new therapies for cardiovascular diseases and other conditions, in which macrophage activity impacts outcomes.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.130.suppl_2.18687
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1466401-X
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  • 2
    Online Resource
    Online Resource
    Abstract 175: Dynamin-Related Protein 1 Regulates Proteostasis and Proprotein Convertase Subtilisin/Kexin Type 9 Secretion
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: Dysfunctional protein homeostasis (proteostasis) contributes to cardiovascular and metabolic disorders. We and others associated the mitochondrial fission protein, Dynamin-related protein 1 (DRP1) with cardiometabolic disease. Liver DRP1-deficiency reduces serum lipids and very-low density lipoprotein secretion in high-fat fed mice; whether DRP1 mediates these effects via proteostasis regulation is unknown. Approach and Results: Using mass spectrometry integrated with network analysis to map the human liver secretome, we found DRP1 associated with cardiovascular disease modules and lipid pathways. Electron microscopy revealed human liver DRP1 at mitochondria, cytosol, vesicles, endoplasmic reticulum (ER), and clustered at membrane tethered to ER exit sites. DRP1 small molecule inhibition (Mdivi-1) or CRISPR/Cas9-mediated DRP1 deletion in human liver cells, and Drp1 -liver deficiency in mice reduced autophagic flux without impairing the amino acid metabolome, or activating the autophagy inhibitor, mammalian target of rapamycin complex 1. DRP1 partially co-localized and co-immunoprecipitated with the ER trafficking and autophagy regulator, Syntaxin 17, in human liver tissue and cells. DRP1 inhibition reduced Proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion in human liver cells and mice (-78.5%), and altered trafficking of the PCSK9-binding and ER maintenance chaperone, Glucose-regulated protein 94. Co-treating human liver cells with Mdivi-1 and proteasome inhibitor (MG132), non-transcriptionally increased intracellular PCSK9, while maintaining Mdivi-1-mediated reduced PCSK9 secretion. Conclusions: We propose a novel function of DRP1 in the regulation of proteostasis, wherein DRP1 may cluster, then tether and/or constrict nascent autophagy-associated membrane at the ER via its interaction with Syntaxin 17. DRP1 inhibition likely reduces lipoprotein and PCSK9 secretion in part by impairing autophagic flux leading to compensatory chaperone-mediated proteasomal degradation for ER maintenance. Proteostasis regulation and the cellular function of DRP1 is more complex than previously thought, potentially providing new avenues to therapeutically target cardiometabolic disease.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.175
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494427-3
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  • 3
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    Online Resource
    Abstract 595: Transcriptional Control of Intestinal Cholesterol Absorption, Adipose Energy Expenditure and Lipid Handling by Sortilin
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional lipid uptake, storage, and metabolism contribute to several major human diseases including atherosclerosis and obesity. Sortilin associates with cardiovascular disease; however, the role of Sortilin in adipose tissue and lipid metabolism remains unclear. Approach and Results: Here we show that in the low-density lipoprotein receptor-deficient (Ldlr -/- ) atherosclerosis model, Sortilin deficiency ( Sort1 -/- ) in female mice inhibits intestinal Niemann-Pick type C1-Like 1 (Npc1l1) expression (-60.6 %, p 〈 0.01), reduces body (-17.2 %, p 〈 0.01) and white adipose tissue weight (-35.2 %, p 〈 0.05), and improves brown adipose tissue function partially via transcriptional downregulation of Krüppel-like factor 4 and Liver X receptor (Figure). Female Ldlr -/- Sort1 -/- mice on a high fat/cholesterol diet had elevated plasma Fibroblast growth factor 21 (+89.1 %, p 〈 0.05) and Adiponectin (+37.7 %, p 〈 0.01), an adipokine that when reduced is associated with obesity and cardiovascular disease related factors. Additionally, Sortilin deficiency suppressed cholesterol absorption in both human colon Caco-2 cells (-16.5 %, p 〈 0.05) and mouse ex vivo intestinal tissue (-16.9 %, p 〈 0.05) in a similar manner to treatment with the Npc1l1 inhibitor - ezetimibe. Conclusions: Together our findings support a novel role of Sortilin in energy regulation and lipid homeostasis in female mice, which may be a potential therapeutic target for obesity and cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.595
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494427-3
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  • 4
    Online Resource
    Online Resource
    Abstract 329: Systems-based Target Discovery Reveals PPARa as a Key Metabolic Regulator for Macrophage Activation in Vein Graft Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objectives: Vein graft (VG) failure rates after surgical bypass for PAD remain high, which can cause limb loss. Yet, the underlying mechanisms for VG lesion development remain obscure. We took a systems approach to explore key pathways in a mouse model. Approach and Results: We implanted the inferior vena cava into the left carotid artery of fat-fed Ldlr-/- mice and monitored lesion development up to 4 weeks post-surgery. Unbiased proteomic profiling followed by hierarchical clustering showed distinct clusters. One protein cluster is decreased in vein grafts with overt lesions (poor outcome) relative to the group of non-diseased veins devoid of lesions and vein grafts with minimal lesion (favorable outcome). Conversely, this can be viewed as increased in the “favorable” outcome group. Using the “favorable outcome” predominant protein cluster, network analysis and pathway enrichment identified PPARα pathway as a top-ranked key hub node with high betweeness centrality measure. This implies that PPARα may play a key regulatory role in limiting lesion severity. We examined whether network-based prediction of PPARα can also serve as a therapeutic target to attenuate the development of experimental VG lesions. A blinded in vivo loss-of-function study using PPARα siRNA encapsulated in macrophage-targeted lipid nanoparticles (LNP) demonstrated higher plaque volume as seen by 3D ultrasound and histologic morphometry in the test group (n=7) versus the control group (n=8). In contrast, a randomized drug study on another set of VG mice using the new PPARα-selective agonist pemafibrate demonstrated less plaque lesions and macrophage accumulation in the drug group (n=11) compared to the control group (n=11). In vitro validation studies (alongside loss-of-function) including high-throughput qPCR, single cell qPCR, CyTOF, ELISA, FACS, and metabolic assays all suggested that pemafibrate-induced PPARα activation promotes a phenotype shift of activated macrophages into a less inflammatory state through metabolic reprogramming. Conclusion: Systems-based target discovery on VG demonstrates that PPARα agonism reduces lesion development and inflammatory burden. Targeting this pathway might furnish a novel therapeutic option to prevent VG lesion development.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.329
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494427-3
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  • 5
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    Online Resource
    Abstract 708: Using Global Proteomics and Network Science to Explore Therapeutic Targets for Abdominal Aortic Aneurysm (AAA)
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. Suppl_1 ( 2018-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
    Abstract: Objective: To understand mechanisms critical to aneurysm development and identify potential therapeutic targets, we performed global proteomics and network analysis in mouse models of AAA. Methods and Results: AAAs were produced by luminal perfusion of the infrarenal aorta of C57BL/6 (wild-type) mice with elastase or subcutaneous infusion of angiotensin II (AngII) in Apoe-/- and Ldlr-/- mice (on congenic C57BL/6 background). Aortas were harvested at two intervals corresponding to developing or end-point aneurysm phenotypes that are specific to each model (n=3 for each procedure, interval, and genotype). Aortas were dissected into 8 segments spanning the arch to infrarenal portion, resulting in combined 288 aortic segments for label-free proteomics. Proteins were classified as significantly correlated to aneurysm according to their fold-change over control. Additional correlations were derived from a high-dimensional data analysis tool (“Xina”), developed in our laboratory, which enables clustering of proteins according to model, genotype, aortic region, and interval. Using our criteria, we identified lists of 159 proteins in the Apoe-/- and 158 proteins in the Ldlr-/- mice (AngII infused), and 173 proteins in wild-type mice (elastase perfused). Network analysis of these protein lists reveal commonalities between the models to include protein pathways related to protein translation, immune function, platelet activation, and extracellular matrix organization. Pathways enriched following AngII infusion included phagosome function and platelet aggregation, while pathways enriched in the elastase model included apoptosis, smooth muscle cell contraction, and Fc gamma R-mediated phagocytosis. Conclusion: Identification of pathways and proteins shared among these models may present master regulators of aneurysmal events and identify therapeutic targets. Conversely, identifying aneurysmal events unique to each model will provide valuable information regarding the model(s) chosen for use in a study and help contextualize model-specific findings.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.38.suppl_1.708
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
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  • 6
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    Online Resource
    Abstract 647: Induction of Cardiovascular Calcification in Non-transgenic Mice via a Single Injection of Pcsk9 Adeno-associated Viral Vector
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 36, No. suppl_1 ( 2016-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
    Abstract: Background: Studying atherosclerotic calcification in vivo requires mouse models with genetic deletion of low-density lipoprotein receptor (Ldlr) or apolipoprotein E. A previous study showed a rapid induction of atherosclerosis by proprotein convertase subtilisin/kexin type 9 (PCSK9) in mice. Here, we hypothesize that this method is a useful in vivo tool to study cardiovascular calcification in non-genetically modified C57BL/6 mice. Results: 10 week old C57BL/6 mice received a single tail vein injection of recombinant adeno-associated viral vector (AAV) encoding PCSK9 (rAAV8/D377Y-mPCSK9). Ldlr -/- and saline injected C57BL/6 mice served as controls. Mice consumed a high-fat, high-cholesterol (HF/HC) diet for 15-20 weeks. PCSK9 and total cholesterol serum levels were significantly increased within one week after injection and maintained for 20 weeks (cholesterol: 82 mg/dL to 820 mg/dL, p 〈 0.01; PCSK9: 0.14 μg/ml to 20 μg/ml, p 〈 0.01). Total cholesterol levels remained 20-30% lower than those of of Ldlr -/- mice. Atherosclerotic lesion size was similar between PSCK9 and Ldlr -/- mice. Saline injected mice did not show any lesions. Plaque collagen content was 31.9%±6.6 in PCSK9 mice and 62.9%±16.6 in Ldlr -/- mice at 15 weeks of HF/HC diet (p=0.01). However, by 20 weeks, the PCSK9 mice had 57.9%±18.6 plaque collagen, suggesting a different stage of plaque progression. Fluorescence reflectance imaging of a near infrared calcium tracer in intact arteries detected 0.4%±0.4 aortic calcification in PCSK9 mice and 9.7%±1.6 in Ldlr -/- mice at 15 weeks of HF/HC diet (p=0.01); by 20 weeks, the PCSK9 mice had 5.3%±1.0 aortic calcification. Tissue non-specific alkaline phosphatase activity positive lesion area was 7.9%±4.0 and 8.3%±2.6 in PCSK9 mice and 10.8%±2.5 and 12.7%±1.7in Ldlr -/- mice at 15 and 20 weeks, respectively. Immunofluorescence analysis demonstrated accumulation of CD68 and RUNX2-positive cells in the plaques of PCSK9 mice similar to Ldlr -/- . Conclusion: While injection of recombinant AAV encoding PCSK9 into C57BL/6 mice induces atherosclerotic calcification with slower sclerotic plaque remodeling compared to Ldlr -/- mice, it may serve as a useful tool to study cardiovascular calcification in mice independent of their genetic background.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.36.suppl_1.647
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1494427-3
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  • 7
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    Online Resource
    Abstract 452: Longitudinal Visualization of Calcification Genesis and Growth in vivo : Novel Implications for Plaque Vulnerability
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 36, No. suppl_1 ( 2016-05)
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
    Abstract: Background: Clinical evidence links arterial calcification and cardiovascular risk. Fibrous cap microcalcifications can promote atherosclerotic plaque failure, and large calcifications can stabilize the plaque. Therefore, calcification morphology can determine cardiovascular morbidity, but temporal patterns of calcific mineral deposition and growth remain unknown. Results: Apolipoprotein E-deficient ( Apoe-/- ) mice on an atherogenic diet develop plaque calcification. Longitudinal studies were performed using two different fluorescent calcium tracers injected intravenously into Apoe-/- mice: calcein injection following 18 weeks of atherogenic diet (n=7) and alizarin red S injection into the same mice 1 (n=4) or 3 (n=3) weeks later. Imaging green (calcein) and red (alizarin red S) fluorescence provided snapshots of aortic calcification at 18, 19, and 21 weeks. Observations within histological sections revealed green microcalcifications at 18 weeks embedded within alizarin red stained larger calcifications that were formed by 19 weeks (a). These data demonstrate that microcalcifications present at the start of calcification become the core of the larger calcifications that develop over time. Serial histological sections from aortic root to arch (b) were digitally reconstructed into 3D volumes (c) to reveal total calcific burden and localization within the aortic wall (d). Total calcification volume increased at a significant rate of 6.0x10 6 μm 3 per week (R 2 =0.99, p=0.007) and progressed from aortic arch to aortic root over time (p 〈 0.001). Observations closely match calcification morphologies found by micro-computed tomography of human coronary arteries. Conclusion: Temporal and spatial understanding arterial calcification growth is crucial given the link between mineral morphology and cardiovascular risk, and these techniques provide a method for testing therapeutic approaches to control calcification morphology over time in situ .
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/atvb.36.suppl_1.452
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
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  • 8
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    Online Resource
    Current Trends and Future Perspectives of State-of-the-Art Proteomics Technologies Applied to Cardiovascular Disease Research
    Japanese Circulation Society ; 2016
    In:  Circulation Journal Vol. 80, No. 8 ( 2016), p. 1674-1683
    Details
    In: Circulation Journal, Japanese Circulation Society, Vol. 80, No. 8 ( 2016), p. 1674-1683
    Type of Medium: Online Resource
    ISSN: 1346-9843 , 1347-4820
    URL: Article
    DOI: 10.1253/circj.CJ-16-0499
    Language: English
    Publisher: Japanese Circulation Society
    Publication Date: 2016
    detail.hit.zdb_id: 2084830-4
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  • 9
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    Online Resource
    Abstract 12839: Integrated Multi-Omics and Single Nucleus Transcriptomics Highlight Enhanced Adaptive Immune Responses in Human Bicuspid Aortic Valve Stenosis
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Circulation Vol. 146, No. Suppl_1 ( 2022-11-08)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 146, No. Suppl_1 ( 2022-11-08)
    Abstract: Introduction: Bicuspid aortic valve (BAV) is the most common congenital cardiac defect, occurring in 1.5% of humans. Due to unknown pathogenic mechanisms, over 70% of those with BAV develop calcific aortic valve disease (CAVD). These patients require valve replacement 25x more frequently and a decade earlier than those with a tricuspid aortic valve (TAV). Objective: Identify cellular and molecular drivers of accelerated disease in BAV-CAVD. Methods: Small RNA-seq, RNA-seq, and proteomics were performed on 70 human aortic valves (11 non-diseased TAVs; fibrotic and calcific stages of 32 TAVs and 27 BAVs excised for CAVD). Single nuclei RNA-seq (snRNA-seq) was completed on 54,608 nuclei from 13 additional human valves (4 non-diseased TAVs; 5 TAVs and 4 BAVs with CAVD). Results: 4,938 miRs, transcripts, and proteins were differentially enriched between stages of BAV- and TAV-CAVD (q 〈 0.05). Multi-omics data, CT-derived valve calcification, and 29 clinical parameters were integrated by latent factor analysis. Protein-protein interaction networks revealed significantly elevated adaptive immune responses in BAV-CAVD: T cell/B cell inflammatory activation was enhanced and SLIT-ROBO signaling disrupted in diseased BAVs. snRNA-seq identified 10 major cell types in human aortic valves: valvular interstitial cells (65% of cells; 3 states), endothelial cells (10%; 2), macrophages (13%), T cells (8%; 2), and B cells (3%; 2). CAVD drove differentiation of dual side-specific endothelial subpopulations, enrichment of CARMN/CACNA1C/ACTA2-high interstitial cells, and substantial immune cell accumulation. B cells were further enriched in BAV- vs. TAV-CAVD. Conclusions: Adaptive immunity underpins molecular differences in BAV- vs. TAV-CAVD and is a novel avenue for tailored pharmacotherapy. We potentiate targeting of key cellular subpopulations by defining the dissociation bias-free transcriptional and cellular diversity of human CAVD at single-cell resolution.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.146.suppl_1.12839
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1466401-X
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  • 10
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    Online Resource
    Osteogenesis Associates With Inflammation in Early-Stage Atherosclerosis Evaluated by Molecular Imaging In Vivo
    Ovid Technologies (Wolters Kluwer Health) ; 2007
    In:  Circulation Vol. 116, No. 24 ( 2007-12-11), p. 2841-2850
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. 24 ( 2007-12-11), p. 2841-2850
    Abstract: Background— Arterial calcification is associated with cardiovascular events; however, mechanisms of calcification in atherosclerosis remain obscure. Methods and Results— We tested the hypothesis that inflammation promotes osteogenesis in atherosclerotic plaques using in vivo molecular imaging in apolipoprotein E −/− mice (20 to 30 weeks old, n=35). A bisphosphonate-derivatized near-infrared fluorescent imaging agent (excitation 750 nm) visualized osteogenic activity that was otherwise undetectable by x-ray computed tomography. Flow cytometry validated the target specifically in osteoblast-like cells. A spectrally distinct near-infrared fluorescent nanoparticle (excitation 680 nm) was coinjected to simultaneously image macrophages. Fluorescence reflectance mapping demonstrated an association between osteogenic activity and macrophages in aortas of apolipoprotein E −/− mice ( R 2 =0.93). Intravital dual-channel fluorescence microscopy was used to further monitor osteogenic changes in inflamed carotid arteries at 20 and 30 weeks of age and revealed that macrophage burden and osteogenesis concomitantly increased during plaque progression ( P 〈 0.01 and P 〈 0.001, respectively) and decreased after statin treatment ( P 〈 0.0001 and P 〈 0.05, respectively). Fluorescence microscopy on cryosections colocalized near-infrared fluorescent osteogenic signals with alkaline phosphatase activity, bone-regulating protein expression, and hydroxyapatite nanocrystals as detected by electron microscopy, whereas von Kossa and alizarin red stains showed no evidence of calcification. Real-time reverse-transcription polymerase chain reaction revealed that macrophage-conditioned media increased alkaline phosphatase mRNA expression in vascular smooth muscle cells. Conclusions— This serial in vivo study demonstrates the real-time association of macrophage burden with osteogenic activity in early-stage atherosclerosis and offers a cellular-resolution tool to identify preclinical microcalcifications.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/CIRCULATIONAHA.107.732867
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2007
    detail.hit.zdb_id: 1466401-X
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