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 Singh"],"technology_type":["Mass Spectrometry","Data-independent acquisition"],"software":[""],"submitter_keywords":["Plasma","Nanoparticle","Atherosclerosis","Proteomics","Dia"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD063218"],"tissue":["Blood Plasma"],"sample_protocol":["Plasma samples were processed with ProteographTM Product Suite using the Proteograph XT Assay,35 using 75 µl of each plasma sample that was mixed with 165 µl of Reconstitution Buffer A (S55R3090) to yield a final volume of 240 µl and were then transferred to Seer Sample Tubes for processing with the Proteograph XT Assay kit (S55R1100). Plasma proteins were quantitatively captured in nanoparticle associated protein coronas. Proteins were subsequently denatured, reduced, alkylated and subjected to proteolytic digestion (trypsin and Lys-C). Peptides were purified and yields were determined (Thermo Fisher Scientific catalog #23290). Peptides were dried down overnight with a vacuum concentrator and reconstituted with a reconstitution buffer to a concentration of 50 ng/µl. For direct digestion of 30 µl neat plasma samples, proteins were denatured, reduced, alkylated and subjected to proteolytic digestion (Trypsin and Lys-C) for 3 hours at 37ºC. Peptides were purified by solid phase extraction and yields were determined (Thermo Fisher Scientific catalog #23290). For data-independent acquisition (DIA), 8 µL of reconstituted peptide mixture from each nanopartilce preparation was analyzed resulting in a constant 400 ng load on column for nanoparticle A and nanoparticle B samples. Each sample was analyzed with a Vanquish NEO nanoLC system coupled with a Orbitrap TM Astral TM(Thermo Fisher Scientific) mass spectrometer using a trap-and-elute configuration. First, the peptides were loaded onto an AcclaimTM PepMapTM 100 C18 (0.3 mm ID x 5 mm) trap column and then separated on a Gen1 50 cm µPACTM analytical column (Thermo Fisher Scientific ) at a flow rate of 1 µl/min using a gradient of 4 – 35% mobile phase B (acetonitrile/0.1% formic acid) mixed into mobile phase A (water/0.1% formic acid) over 21 minutes, resulting in a 26-minute run time. The mass spectrometer was operated in DIA mode. MS1 scans were performed in the Orbitrap detector at 240, 000 resolution, every 0.6 seconds with a 5 ms ion injection time or 500% automatic gain control (AGC; 500,000 ion) target. For DIA experiment, two-hundred fixed DIA window covering 380 Th – 980 Th mass range were collected at the Astral detector per cycle with 3 Th precursor isolation windows, 25% normalized collision energy, and 5 ms ion injection times with a 500% (50,000 ions) active gain control maximum. MS2 scans were collected from m/z 150-2000. Window placement optimization was turned on. A source voltage of 1500 V and an ion transfer tube temperature of 300°C were used for all experiments."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["DIA data was processed using ProteographTM Analysis Suite (PAS). The spectra were processed using the DIA-NN search engine (version 1.8.1) in library-free mode searching MS/MS spectra against an in silico generated spectral library using the Uniprot mouse database (UP000000589_10090). Library-free search parameters include trypsin protease, 1 missed cleavage, N-terminal methionine excision, fixed modification of Cys carbamidomethylation, peptide length of 7-30 amino acids, precursor range of m/z 300-1800, and fragment ion range of m/z 200-1800. MS1 and MS2 mass accuracy was set to 3 and 8 ppm, respectively. Precursor and Protein Group false-discovery rate (FDR) thresholds were set at 1%. Quantiﬁcation was performed on summed abundances of all unique peptides considering only precursors passing the FDR thresholds. PAS summarizes all nanoparticle values for a single protein into a single quantitative value. Specifically, a single protein may have been measured two times, once for each nanoparticle. To derive the single measurement value, PAS uses a maximum representation approach, whereby the single quantification value for a particular peptide or protein group represents the quantitation value of the nanoparticle most frequently measured across all samples."],"omics_type":["Proteomics"],"labhead":["Masanori Aikawa"],"instrument_platform":[""],"labhead_affiliation":["Center for Interdisciplinary Cardiovascular Sciences, Department of Medicine, Briham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"submitter_mail":["sasingh@bwh.harvard.edu"],"publication":["42617360 Delwarde C,Matamalas JT,Chelvanambi S,Kasai T,Shlayen G,Santinelli-Pestana DV,Zamani M,Aikawa E,Aikawa M,Singh SA Nanoparticle-Enabled Plasma Proteomics of Experimental Atherosclerosis in Mice. JACC Basic Transl Sci. 2026 Aug 19 11(9):101649 10.1016/j.jacbts.2026.101649"],"submitter_affiliation":["Brigham and Women's Hospital, Harvard Medical School"],"submitter_country":["United States"],"pubmed_abstract":["Dyslipidemia, marked by elevated low-density lipoprotein cholesterol, is a major risk factor for coronary heart disease. Mouse experimental systems, such as Ldlr<sup>-/-</sup> mice that develop atherosclerosis and metabolic disorders when fed a high-fat diet (HFD), are crucial for studying disease mechanisms and identifying potential biomarkers. Using recent nanoparticle-dependent enrichment of plasma proteins and mass spectrometry, we quantified 5,080 plasma proteins from Ldlr<sup>-/-</sup> mice fed a chow or HFD for 3 or 6 months. Proteins with sustained enrichment in HFD were indicative of liver cell subtypes, whereas proteins that increased from 3 to 6 months were indicative of inflammation and endothelial activation. Proteins/genes from human cardiovascular genomic and proteomic studies were also detected in the plasma and aorta including MMP12, LPL, and HP that increased with HFD. These data provide many avenues for understanding disease pathology and uncovering novel molecular contributors to cardiovascular diseases."],"pubmed_title":["Nanoparticle-Enabled Plasma Proteomics of Experimental Atherosclerosis in Mice."],"pubmed_authors":["Delwarde Constance C, Matamalas Joan T JT, Chelvanambi Sarvesh S, Kasai Taku T, Shlayen Gabriel G, Santinelli-Pestana Diego V DV, Zamani Maedeh M, Aikawa Elena E, Aikawa Masanori M, Singh Sasha A SA"],"additional_accession":[]},"is_claimable":false,"name":"Nanoparticle-enabled plasma proteomics of a preclinical atherosclerosis model reveals common signatures with human disease","description":"Coronary heart disease (CHD) accounts for one-third of deaths in the United States, with an annual economic burden exceeding $400 billion. Elevated plasma levels of low-density lipoprotein-cholesterol (LDL-C) is a major risk factor for CHD, through its promotion of atherosclerosis. Mutations in the LDL receptor (LDLR) are causal for familial hypercholesterolemia, inciting the Ldlr-/- murine model for atherosclerosis studies. Despite >3,000 reports using this model, the technical challenge of low volume blood draws from mice, on top of the limited detection range in plasma, have impeded efforts to identify circulating disease drivers. The recent advent of nanoparticle-dependent biofluid proteomics has enabled more sensitive monitoring of mouse tissue-associated disease drivers in plasma, offering insights into their relevance to human atherosclerosis.","dates":{"publication":"2026-08-20","submission":"2025-04-23"},"accession":"PXD063218","cross_references":{"TAXONOMY":["NEWT:3555","NEWT:71647","NEWT:330879","NEWT:35554","NCBITaxon:12939","NEWT:32046","NEWT:544496","NEWT:59529","NEWT:2042546","NEWT:32049","NEWT:1392696","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:45351","NEWT:445974","NEWT:43179","NEWT:180454","NEWT:5722","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:10245","NEWT:55153","NEWT:10244","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:351581","NEWT:43186","NEWT:428146","NEWT:111205","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:498019","NEWT:1351","NEWT:1438992","NEWT:1352","NEWT:2649997","NEWT:1147161","NEWT:661410","NEWT:638632","NEWT:263737","NEWT:224326","NEWT:1333499","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:5702","NEWT:95648","NEWT:1589","NEWT:135622","NEWT:1349","NEWT:67352","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:383379","NEWT:1401257","NEWT:418106","NEWT:10029","NEWT:913645","NEWT:44491","NEWT:641809","NEWT:27933","NEWT:556484","NEWT:317447","NEWT:4688","NEWT:7955","NEWT:111225","NEWT:7719","NEWT:7959","NEWT:2261","NEWT:868565","NEWT:31156","NEWT:3112","NEWT:79329","NEWT:4442","NEWT:31155","NEWT:192875","NEWT:1214915","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:284218","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:1316931","NEWT:224308","NEWT:3347","NEWT:511145","NEWT:160621","NEWT:212790","NEWT:931281","NEWT:4432","NEWT:5762","NEWT:5763","NEWT:658457","NEWT:1310161","NEWT:77133","NEWT:295358","NEWT:145481","NCBITaxon:79824","NEWT:2246","NEWT:2652724","NEWT:1912919","NEWT:5757","NEWT:68415","NCBITaxon:4563","NEWT:5755","NEWT:44688","NEWT:44689","NEWT:44447","NEWT:752555","NEWT:498211","NEWT:5759","NEWT:347256","NEWT:1736231","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:1392","NEWT:498217","NEWT:498216","NEWT:2242","NEWT:11320","NEWT:286","NEWT:391619","NEWT:246196","NEWT:287","NEWT:246197","NEWT:1367269","NEWT:145458","NEWT:633149","NEWT:1149786","NEWT:10239","NEWT:68895","NEWT:44685","NEWT:161934","NEWT:4897","NEWT:1148","NEWT:5744","NEWT:72901","NEWT:213863","NEWT:5508","NEWT:3329","NEWT:5507","NEWT:410661","NEWT:55571","NEWT:35500","NEWT:1235816","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:4896","NEWT:1287689","NEWT:1390","NEWT:11557","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:294","NEWT:1773","NEWT:1182590","NEWT:3712","NEWT:82380","NEWT:3711","NEWT:935293","NEWT:375146","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:1772","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:263","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:11988","NEWT:284812","NEWT:8175","NEWT:400667","NEWT:43330","NEWT:980415","NEWT:1603293","NEWT:408169","NEWT:44664","NEWT:47946","NEWT:459758","NEWT:3702","NEWT:1245466","NEWT:243277","NEWT:1246791","NEWT:7067","NEWT:118694","NEWT:586722","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:274","NEWT:7070","NCBITaxon:287","NEWT:408172","NEWT:408170","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1436733","NEWT:460519","NEWT:1247411","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:9483","NEWT:333760","NEWT:56636","NEWT:1513458","NEWT:1233681","NCBITaxon:40559","NEWT:506599","NEWT:2853422","NEWT:81077","NEWT:84588","NEWT:1679718","NEWT:480","NEWT:65349","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:300852","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:95486","NEWT:508771","NEWT:1883446","NEWT:253","NCBITaxon:2759","NEWT:1233435","NEWT:93061","NEWT:93062","NEWT:34613","NCBITaxon:4932","NEWT:109760","NEWT:943274","NEWT:644223","NEWT:235443","NEWT:108458","NEWT:5936","NEWT:272623","NEWT:272624","NEWT:320637","NEWT:2719099","NEWT:886559","NEWT:3750","NEWT:55521","NEWT:983964","NEWT:118499","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:1130798","NEWT:55529","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:476272","NEWT:3747","NEWT:195051","NEWT:3988","NEWT:1116234","NEWT:561007","NEWT:1255228","NEWT:649908","NEWT:410289","NEWT:373153","NEWT:3983","NEWT:203696","NEWT:352472","NEWT:1071661","NEWT:1202532","NEWT:360094","NEWT:470","NEWT:41364","NEWT:5911","NEWT:1313","NEWT:1218097","NEWT:1080348","NCBITaxon:50557","NEWT:39251","NEWT:39491","NEWT:212142","NCBITaxon:5811","NEWT:29491","NEWT:101841","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:153009","NEWT:261756","NEWT:571256","NEWT:40483","NEWT:63366","NEWT:63367","NEWT:688333","NEWT:215402","NCBITaxon:548681","NEWT:318586","NCBITaxon:5820","NEWT:1547","NEWT:272634","NEWT:198107","NEWT:9031","NEWT:27292","NEWT:1872122","NEWT:1308","NEWT:7091","NEWT:1034015","NEWT:760568","NEWT:141262","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:4087","NEWT:9778","NEWT:306","NEWT:150475","NEWT:303","NEWT:267872","NEWT:97477","NEWT:7111","NEWT:347515","NEWT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