Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related to Levels of Plasma Insulin
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{"title"=>"Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin", "type"=>"journal", "authors"=>[{"first_name"=>"Sara", "last_name"=>"Hägg", "scopus_author_id"=>"36010457900"}, {"first_name"=>"Mehran", "last_name"=>"Salehpour", "scopus_author_id"=>"6601993822"}, {"first_name"=>"Peri", "last_name"=>"Noori", "scopus_author_id"=>"8665187500"}, {"first_name"=>"Jesper", "last_name"=>"Lundström", "scopus_author_id"=>"24067552600"}, {"first_name"=>"Göran", "last_name"=>"Possnert", "scopus_author_id"=>"56235579400"}, {"first_name"=>"Rabbe", "last_name"=>"Takolander", "scopus_author_id"=>"7005069498"}, {"first_name"=>"Peter", "last_name"=>"Konrad", "scopus_author_id"=>"7005974517"}, {"first_name"=>"Stefan", "last_name"=>"Rosfors", "scopus_author_id"=>"7003481816"}, {"first_name"=>"Arno", "last_name"=>"Ruusalepp", "scopus_author_id"=>"6506289914"}, {"first_name"=>"Josefin", "last_name"=>"Skogsberg", "scopus_author_id"=>"6602640475"}, {"first_name"=>"Jesper", "last_name"=>"Tegnér", "scopus_author_id"=>"7004724921"}, {"first_name"=>"Johan", "last_name"=>"Björkegren", "scopus_author_id"=>"6602923495"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"79954539936", "pmid"=>"21490968", "isbn"=>"1932-6203", "pui"=>"361607479", "issn"=>"19326203", "scopus"=>"2-s2.0-79954539936", "doi"=>"10.1371/journal.pone.0018248"}, "id"=>"4bc50678-9b01-301f-8a51-87b3b884978e", "abstract"=>"BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14)C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.\\n\\nMETHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14)C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.\\n\\nCONCLUSIONS/SIGNIFICANCE: Our results show, for the first time, that plaque age, as judge by relative incorporation of (14)C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.", "link"=>"http://www.mendeley.com/research/carotid-plaque-age-feature-plaque-stability-inversely-related-levels-plasma-insulin", "reader_count"=>21, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>11, "Agricultural and Biological Sciences"=>5, "Arts and Humanities"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/785479"], "description"=>"<p>To identify groups of functionally related genes important for plaque\n age, a two-way clustering approach was used <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018248#pone.0018248-Hagg1\" target=\"_blank\">[14]</a>. In the first step,\n the cluster algorithm is used to determine the total number of\n functionally related gene groups (i.e., gene clusters) in the carotid\n plaques calculated from 24 gene expression profiles. Eight gene clusters\n were identified. In the second step, one cluster\n (n = 13 RefSeqs/genes) segregated the carotid\n stenosis patients into two groups that differed significantly in plaque\n age (p = 0.04), suggesting that these genes could\n be involved in this plaque formation. Eight of the 13 genes were related\n to immune or inflammatory processes linked to atherosclerosis.</p>", "links"=>[], "tags"=>["mrna", "segregating", "patients", "plaque"], "article_id"=>455838, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018248.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_mRNA_cluster_segregating_patients_according_to_plaque____ages_/455838", "title"=>"An mRNA cluster segregating patients according to plaque\n ages.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-07 01:37:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/393356", "https://ndownloader.figshare.com/files/393365", "https://ndownloader.figshare.com/files/393377", "https://ndownloader.figshare.com/files/393395", "https://ndownloader.figshare.com/files/393408", "https://ndownloader.figshare.com/files/393419", "https://ndownloader.figshare.com/files/393432", "https://ndownloader.figshare.com/files/393440", "https://ndownloader.figshare.com/files/393454", "https://ndownloader.figshare.com/files/393466", "https://ndownloader.figshare.com/files/393475", "https://ndownloader.figshare.com/files/393485"], "description"=>"<div><h3>Background</h3><p>The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric <sup>14</sup>C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.</p> <h3>Methodology/Principal Finding</h3><p>The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for <sup>14</sup>C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.</p> <h3>Conclusions/Significance</h3><p>Our results show, for the first time, that plaque age, as judge by relative incorporation of <sup>14</sup>C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.</p> </div>", "links"=>[], "tags"=>["carotid", "plaque", "inversely", "related", "levels", "plasma", "insulin"], "article_id"=>137676, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0018248.s001", "https://dx.doi.org/10.1371/journal.pone.0018248.s002", "https://dx.doi.org/10.1371/journal.pone.0018248.s003", "https://dx.doi.org/10.1371/journal.pone.0018248.s004", "https://dx.doi.org/10.1371/journal.pone.0018248.s005", "https://dx.doi.org/10.1371/journal.pone.0018248.s006", "https://dx.doi.org/10.1371/journal.pone.0018248.s007", "https://dx.doi.org/10.1371/journal.pone.0018248.s008", "https://dx.doi.org/10.1371/journal.pone.0018248.s009", "https://dx.doi.org/10.1371/journal.pone.0018248.s010", "https://dx.doi.org/10.1371/journal.pone.0018248.s011", "https://dx.doi.org/10.1371/journal.pone.0018248.s012"], "stats"=>{"downloads"=>6, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Carotid_Plaque_Age_Is_a_Feature_of_Plaque_Stability_Inversely_Related___to_Levels_of_Plasma_Insulin/137676", "title"=>"Carotid Plaque Age Is a Feature of Plaque Stability Inversely Related\n to Levels of Plasma Insulin", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-04-07 02:07:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/785617"], "description"=>"<p>GT, gamma-glutamyltransferase; ALAT, alanine aminotransferase; HDL,\n high density lipoprotein; LDL, low density lipoprotein; VLDL, very\n low density lipoprotein; TG, triglyceride; HbA1c, glycated\n hemoglobin; CRP, C-reactive protein; ASAT, aspartate\n aminotransferase; LDL, low density lipoprotein.</p>", "links"=>[], "tags"=>["pearson", "correlations", "plaque"], "article_id"=>455976, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018248.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Univariate_Pearson_correlations_with_plaque_age_/455976", "title"=>"Univariate Pearson correlations with plaque age.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-07 01:39:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/785340"], "description"=>"<p>Representative sections of carotid cores from the terciles of highest\n (slower formation time) and lowest (faster formation time) average\n plaque age (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018248#pone-0018248-t001\" target=\"_blank\">Table\n 1</a>). The IHC analyses were performed on 7-µm\n cryosections and stained (<b>A</b>) for lipids with Oil-Red-O,\n (<b>B</b>) for macrophages with CD68 antibody,\n (<b>C</b>) for collagen with Masson's trichrome, and\n (<b>D</b>) for smooth muscle cells with SM22 antibody. Bar\n charts present mean ± SD.</p>", "links"=>[], "tags"=>["characteristics", "plaque"], "article_id"=>455701, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018248.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IHC_characteristics_of_plaque_age_/455701", "title"=>"IHC characteristics of plaque age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-07 01:35:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/785184"], "description"=>"<p>(<b>A</b>) The bomb curve. Carotid plaque samples were\n <sup>14</sup>C dated using AMS. The cellular birth dates can be\n inferred by determining the time at which <sup>14</sup>C concentration\n of the sample corresponded to the atmospheric concentration, using the\n Levin data as reference bomb curve. (<b>B</b>) Plaque age\n distribution in all carotid stenosis patients\n (n = 29). The interval is from 2–14 years,\n and all but two patients had plaque ages within a 10-year interval.</p>", "links"=>[], "tags"=>["histogram", "carotid", "plaque", "age"], "article_id"=>455540, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018248.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_bomb_curve_and_histogram_of_the_carotid_plaque_age____distribution_/455540", "title"=>"The bomb curve and histogram of the carotid plaque age\n distribution.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-07 01:32:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/785577"], "description"=>"<p>Values are mean ± SD or % (n). HbA1c, glycated\n hemoglobin; VLDL, very low density lipoprotein; LDL, low density\n lipoprotein; HDL, high density lipoprotein; NA, not applicable.</p><p>*p<0.05,</p><p>**p<0.01,</p><p>***p<0.001 vs. high plaque age group.</p>", "links"=>[], "tags"=>["characteristics", "patients", "terciles", "these"], "article_id"=>455927, "categories"=>["Physics", "Biological Sciences", "Physiology", "Genetics", "Immunology"], "users"=>["Sara Hägg", "Mehran Salehpour", "Peri Noori", "Jesper Lundström", "Göran Possnert", "Rabbe Takolander", "Peter Konrad", "Stefan Rosfors", "Arno Ruusalepp", "Josefin Skogsberg", "Jesper Tegnér", "Johan Björkegren"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0018248.t001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_all_patients_and_in_terciles_of_these____patients_/455927", "title"=>"Clinical characteristics of all patients and in terciles of these\n patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-04-07 01:38:47"}

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