Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project
Background and Aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting mon...
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MDPI AG
2023-02-01
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| author | Silverio Sbrana Antonella Cecchettini Luca Bastiani Annamaria Mazzone Federico Vozzi Chiara Caselli Danilo Neglia Alberto Clemente Arthur J. H. A. Scholte Oberdan Parodi Gualtiero Pelosi Silvia Rocchiccioli |
| author_facet | Silverio Sbrana Antonella Cecchettini Luca Bastiani Annamaria Mazzone Federico Vozzi Chiara Caselli Danilo Neglia Alberto Clemente Arthur J. H. A. Scholte Oberdan Parodi Gualtiero Pelosi Silvia Rocchiccioli |
| author_sort | Silverio Sbrana |
| collection | DOAJ |
| description | Background and Aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype—including their phenotypic relationships with platelets, monocytes and lymphocytes—have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS). Methods: In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA. Results: On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count (<i>n°</i>/µL) (<i>p</i> = 0.02), neutrophil/lymphocyte ratio (<i>p</i> = 0.007), neutrophil/platelet ratio (<i>p</i> = 0.01), neutrophil RFI CD11b expression (<i>p</i> = 0.02) and neutrophil–platelet adhesion index (<i>p</i> = 0.01). Significantly positive multiple regression associations of LRNCV values with phenotypic ratios between neutrophil RFI CD11b expression and several lymphocyte and monocyte surface markers were also observed. In the bivariate correlation analysis, a significantly positive association was found between RFI values of neutrophil–CD41a+ complexes and neutrophil RFI CD11b expression (<i>p</i> < 0.0001). Conclusions: These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication. |
| first_indexed | 2024-03-11T08:33:06Z |
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| issn | 2075-1729 |
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| last_indexed | 2024-03-11T08:33:06Z |
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| spelling | doaj.art-fb62d67ff3634693b87d9904e9fa7a692023-11-16T21:41:07ZengMDPI AGLife2075-17292023-02-0113242810.3390/life13020428Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European ProjectSilverio Sbrana0Antonella Cecchettini1Luca Bastiani2Annamaria Mazzone3Federico Vozzi4Chiara Caselli5Danilo Neglia6Alberto Clemente7Arthur J. H. A. Scholte8Oberdan Parodi9Gualtiero Pelosi10Silvia Rocchiccioli11CNR Institute of Clinical Physiology, 54100 Massa, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, ItalyCNR Institute of Clinical Physiology, 54100 Massa, ItalyFondazione Toscana Gabriele Monasterio, 54100 Massa, ItalyCNR Institute of Clinical Physiology, 56124 Pisa, ItalyCNR Institute of Clinical Physiology, 56124 Pisa, ItalyFondazione Toscana Gabriele Monasterio, 56124 Pisa, ItalyFondazione Toscana Gabriele Monasterio, 54100 Massa, ItalyDepartment of Cardiology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsCNR Institute of Clinical Physiology, 56124 Pisa, ItalyCNR Institute of Clinical Physiology, 56124 Pisa, ItalyCNR Institute of Clinical Physiology, 56124 Pisa, ItalyBackground and Aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype—including their phenotypic relationships with platelets, monocytes and lymphocytes—have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS). Methods: In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA. Results: On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count (<i>n°</i>/µL) (<i>p</i> = 0.02), neutrophil/lymphocyte ratio (<i>p</i> = 0.007), neutrophil/platelet ratio (<i>p</i> = 0.01), neutrophil RFI CD11b expression (<i>p</i> = 0.02) and neutrophil–platelet adhesion index (<i>p</i> = 0.01). Significantly positive multiple regression associations of LRNCV values with phenotypic ratios between neutrophil RFI CD11b expression and several lymphocyte and monocyte surface markers were also observed. In the bivariate correlation analysis, a significantly positive association was found between RFI values of neutrophil–CD41a+ complexes and neutrophil RFI CD11b expression (<i>p</i> < 0.0001). Conclusions: These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication.https://www.mdpi.com/2075-1729/13/2/428coronary artery diseaseneutrophilsplateletscytokinesflow cytometrycoronary CT angiography |
| spellingShingle | Silverio Sbrana Antonella Cecchettini Luca Bastiani Annamaria Mazzone Federico Vozzi Chiara Caselli Danilo Neglia Alberto Clemente Arthur J. H. A. Scholte Oberdan Parodi Gualtiero Pelosi Silvia Rocchiccioli Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project Life coronary artery disease neutrophils platelets cytokines flow cytometry coronary CT angiography |
| title | Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project |
| title_full | Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project |
| title_fullStr | Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project |
| title_full_unstemmed | Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project |
| title_short | Association of Circulating Neutrophils with Relative Volume of Lipid-Rich Necrotic Core of Coronary Plaques in Stable Patients: A Substudy of SMARTool European Project |
| title_sort | association of circulating neutrophils with relative volume of lipid rich necrotic core of coronary plaques in stable patients a substudy of smartool european project |
| topic | coronary artery disease neutrophils platelets cytokines flow cytometry coronary CT angiography |
| url | https://www.mdpi.com/2075-1729/13/2/428 |
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