Biomechanics and Inflammation in Atherosclerotic Plaque Erosion and Plaque Rupture: Implications for Cardiovascular Events in Women
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{"title"=>"Biomechanics and inflammation in atherosclerotic plaque erosion and plaque rupture: Implications for cardiovascular events in women", "type"=>"journal", "authors"=>[{"first_name"=>"Ian C.", "last_name"=>"Campbell", "scopus_author_id"=>"36132753900"}, {"first_name"=>"Jonathan D.", "last_name"=>"Suever", "scopus_author_id"=>"26022647000"}, {"first_name"=>"Lucas H.", "last_name"=>"Timmins", "scopus_author_id"=>"15045820500"}, {"first_name"=>"Alessandro", "last_name"=>"Veneziani", "scopus_author_id"=>"7004362913"}, {"first_name"=>"Raymond P.", "last_name"=>"Vito", "scopus_author_id"=>"7003891945"}, {"first_name"=>"Renu", "last_name"=>"Virmani", "scopus_author_id"=>"8215839300"}, {"first_name"=>"John N.", "last_name"=>"Oshinski", "scopus_author_id"=>"7003612131"}, {"first_name"=>"W. Robert", "last_name"=>"Taylor", "scopus_author_id"=>"14626538100"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84909594931", "pui"=>"600373142", "doi"=>"10.1371/journal.pone.0111785", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "sgr"=>"84909594931", "pmid"=>"25365517"}, "id"=>"b1d84ffd-5ee8-3158-8d4f-9c4cebdaccb8", "abstract"=>"OBJECTIVE: Although plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion. METHODS AND RESULTS: We studied a total of 74 human coronary plaque specimens obtained at autopsy. Using lesion-specific computer modeling of solid mechanics, we calculated the stress and strain distribution for each plaque and determined if there were any relationships with markers of inflammation. Consistent with previous studies, inflammatory markers were positively associated with increasing strain in specimens with rupture and thin-cap fibroatheromas. Conversely, overall staining for inflammatory markers and apoptosis were significantly lower in erosion, and there was no relationship with mechanical strain. Samples with plaque erosion most closely resembled those with the stable phenotype of thick-cap fibroatheromas. CONCLUSIONS: In contrast to classic plaque rupture, plaque erosion was not associated with markers of inflammation and mechanical strain. These data suggest that plaque erosion is a distinct pathophysiological process with a different etiology and therefore raises the possibility that a different therapeutic approach may be required to prevent plaque erosion", "link"=>"http://www.mendeley.com/research/biomechanics-inflammation-atherosclerotic-plaque-erosion-plaque-rupture-implications-cardiovascular", "reader_count"=>22, "reader_count_by_academic_status"=>{"Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>5, "Neuroscience"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Netherlands"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1777587"], "description"=>"<p>Von Mises stress and strain excursions were computed for each lesion by breaking down each vessel into a fine-resolution mesh. After sorting the elements in order of increasing stress (or strain) excursion, we pooled results into a baseline group (excursion <0.25) and tertiles or deciles containing an equal number of elements. Thus, higher-numbered groups (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g005\" target=\"_blank\">Figures 5</a>–<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g008\" target=\"_blank\">8</a>) represent regions of higher stress or strain excursion. Negative stress excursion represents stress below the median value, not a negative magnitude of stress.</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227693, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stress_and_strain_excursion_association_with_positive_staining_/1227693", "title"=>"Stress and strain excursion association with positive staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777534"], "description"=>"<p>We segmented histologic cross-sections of human coronary arteries stained with Movat's pentachrome (A) in order to determine their composition (B) on a lesion-specific basis. Based on staining color, we identified whether tissues were fibrous, cellular, lipid/necrotic core, or calcified. We also traced the lumen and external border using an implementation of the Live Wire algorithm <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone.0111785-Chodorowski1\" target=\"_blank\">[12]</a>. We computed and mapped the relative distribution of Von Mises stress and strain for each lesion. Shown here are stress (C) and strain (D) maps, displayed as excursion (normalized difference from the median).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227656, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_segmentation_and_computational_modeling_/1227656", "title"=>"Histology segmentation and computational modeling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777632"], "description"=>"<p>Serial sections of the lesions shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g001\" target=\"_blank\">Figures 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g002\" target=\"_blank\">2</a> were stained for CD68 (Nova Red chromagen) and counterstained with hematoxylin (blue) for nuclei.</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227732, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g011", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_histology_images_of_CD68_staining_/1227732", "title"=>"Representative histology images of CD68 staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777615"], "description"=>"<p>Serial sections of the lesions shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g001\" target=\"_blank\">Figures 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g002\" target=\"_blank\">2</a> were stained for MMP9 (Nova Red chromagen) and counterstained with hematoxylin (blue) for nuclei. Artifacts such as the tissue detachment seen in the TCFA specimen were manually masked to exclude the regions from the final analysis.</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227715, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g010", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_histology_images_of_MMP9_staining_/1227715", "title"=>"Representative histology images of MMP9 staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777593"], "description"=>"<p>Expression of MMP1, a collagenase, across the entire vessel cross-section (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g012\" target=\"_blank\">Figure 12</a>) is significantlylower in plaque erosions than in plaques vulnerable to rupture (left). Whereas sites with elevated mechanical strain are positively associated with the presence of macrophages in ruptured and TCFA (vulnerable) plaques, there is no positive association between strain and macrophages in plaque erosions and thick-cap fibroatheromas (right).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227700, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g008", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MMP1_expression_depends_on_both_lesion_phenotype_and_mechanical_strain_/1227700", "title"=>"MMP1 expression depends on both lesion phenotype and mechanical strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777591"], "description"=>"<p>MMP9, a gelatinase, expression across the entire vessel cross-section (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g010\" target=\"_blank\">Figure 10</a>) is significantly lower in plaque erosions and thick-cap fibroatheromas (stable plaques) than in TCFA plaques vulnerable to rupture (left). Whereas sites with elevated mechanical strain are positively associated with the presence of MMP9 in ruptured and TCFA (vulnerable) plaques, there is no positive association between strain and MMP9 in plaque erosions and thick-cap fibroatheromas (right).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227697, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g006", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MMP9_expression_depends_on_both_lesion_phenotype_and_mechanical_strain_/1227697", "title"=>"MMP9 expression depends on both lesion phenotype and mechanical strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777562"], "description"=>"<p>Movat's pentachrome images (A) were segmented (B), and maps of the relative distribution of stress excursion (C) and strain excursion (D) were created using identical techniques to those in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g001\" target=\"_blank\">Figure 1</a>.</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227682, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g002", "stats"=>{"downloads"=>2, "page_views"=>152, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_images_of_thin_cap_fibroatheroma_TCFA_and_thick_cap_fibroatheroma_lesions_/1227682", "title"=>"Representative images of thin-cap fibroatheroma (TCFA) and thick-cap fibroatheroma lesions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777589"], "description"=>"<p>TUNEL staining for apoptosis (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g009\" target=\"_blank\">Figure 9</a>) expression across the entire vessel cross-section is significantly lower in plaque erosions and thick-cap fibroatheromas (stable plaques) than in ruptured and TCFA plaques (left). Whereas sites with elevated mechanical strain are positively associated with the presence of apoptosis in ruptured and TCFA (vulnerable) plaques, there is no positive association between strain and apoptosis in plaque erosions and thick-cap fibroatheromas (right).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227695, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Apoptosis_expression_depends_on_both_lesion_phenotype_and_mechanical_strain_/1227695", "title"=>"Apoptosis expression depends on both lesion phenotype and mechanical strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777582"], "description"=>"<p>Many histology specimens suffered from fixation and embedding artifacts, such as the vessel at left, which is horizontally compressed relative to its <i>in vivo</i> conformation where the lumen would be mostly circular. Consequently, the computed stress and strain distributions were skewed in regions of high deformation during computational analysis (middle). Therefore, we “pre-inflated” vessels by simulating pressure normal to the lumen, allowing the vessel to deform, and re-meshing the vessel for 10 iterations. This extra processing step minimized the effect of tissue artifacts and presented us with more physiologically-relevant anatomy for our analysis (right).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227688, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Preinflation_technique_for_mechanical_modeling_/1227688", "title"=>"Preinflation technique for mechanical modeling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777603"], "description"=>"<p>Serial sections of the lesions shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g001\" target=\"_blank\">Figures 1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g002\" target=\"_blank\">2</a> were stained for apoptosis using the TUNEL approach (red staining), and differential interference contrast (DIC) is shown for reference. Regions containing coverslip bubbles such as that seen in the erosion specimen were manually masked and excluded from final analysis.</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227709, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g009", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representative_histology_images_of_TUNEL_staining_/1227709", "title"=>"Representative histology images of TUNEL staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/1777592"], "description"=>"<p>CD68, a marker of the macrophages that play a major role in lesion inflammation (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111785#pone-0111785-g011\" target=\"_blank\">Figure 11</a>), median expression across the entire vessel cross-section is lower in plaque erosions and thick-cap fibroatheromas (stable plaques) than in plaques vulnerable to rupture (left). Whereas sites with elevated mechanical strain are positively associated with the presence of macrophages in ruptured and TCFA (vulnerable) plaques, there is no positive association between strain and macrophages in plaque erosions and thick-cap fibroatheromas (right).</p>", "links"=>[], "tags"=>["Women ObjectiveAlthough plaque erosion causes", "Atherosclerotic Plaque Erosion", "plaque rupture", "plaque erosion"], "article_id"=>1227698, "categories"=>["Biological Sciences"], "users"=>["Ian C. Campbell", "Jonathan D. Suever", "Lucas H. Timmins", "Alessandro Veneziani", "Raymond P. Vito", "Renu Virmani", "John N. Oshinski", "W. Robert Taylor"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111785.g007", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD68_expression_depends_on_both_lesion_phenotype_and_mechanical_strain_/1227698", "title"=>"CD68 expression depends on both lesion phenotype and mechanical strain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-03 03:51:49"}

PMC Usage Stats | Further Information

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Relative Metric

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