Pub Date : 2024-09-01Epub Date: 2024-07-25DOI: 10.1161/ATVBAHA.124.321129
Zhen Yuan, Li Shu, Jiantao Fu, Peipei Yang, Yidong Wang, Jie Sun, Mengsha Zheng, Zhenjie Liu, Jin Yang, Jiangping Song, Shen Song, Zhejun Cai
Background: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited.
Methods: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them.
Results: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA.
Conclusions: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.
{"title":"Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.","authors":"Zhen Yuan, Li Shu, Jiantao Fu, Peipei Yang, Yidong Wang, Jie Sun, Mengsha Zheng, Zhenjie Liu, Jin Yang, Jiangping Song, Shen Song, Zhejun Cai","doi":"10.1161/ATVBAHA.124.321129","DOIUrl":"10.1161/ATVBAHA.124.321129","url":null,"abstract":"<p><strong>Background: </strong>Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited.</p><p><strong>Methods: </strong>Using single-cell RNA transcriptomic analysis, we deconstructed the CD45<sup>+</sup> cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them.</p><p><strong>Results: </strong>Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA.</p><p><strong>Conclusions: </strong>Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-03DOI: 10.1161/ATVBAHA.124.320910
Zhen Bouman Chen, Elena Aikawa, Mabruka Alfaidi, Kamilah Ali, Cassandra L Clift, Ebru Erbay, Gabrielle Fredman, Delphine Gomez, Ngan F Huang, Hong S Lu, Patricia K Nguyen, Suellen Darc Oliveira, Paula Rodriguez-Miguelez, Gopika SenthilKumar, Hanrui Zhang
Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender disparities were prevalent in many institutions, recent decades have witnessed significant progress in supporting the career advancement of women faculty in science and academic medicine. However, continued advancement is necessary as previously unrecognized needs and new opportunities for improvement emerge. To identify the needs, opportunities, and potential challenges encountered by women faculty, the Women's Leadership Committee of the Arteriosclerosis, Thrombosis, and Vascular Biology Council developed an initiative termed GROWTH (Generating Resources and Opportunities for Women in Technology and Health). The committee designed a survey questionnaire and interviewed 19 leaders with roles and responsibilities in faculty development from a total of 12 institutions across various regions of the United States. The results were compiled, analyzed, and discussed. Based on our interviews and analyses, we present the current status of these representative institutions in supporting faculty development, highlighting efforts specific to women faculty. Through the experiences, insights, and vision of these leaders, we identified success stories, challenges, and future priorities. Our article provides a primer and a snapshot of institutional efforts to support the advancement of women faculty. Importantly, this article can serve as a reference and resource for academic entities seeking ideas to gauge their commitment level to women faculty and to implement new initiatives. Additionally, this article can provide guidance and strategies for women faculty as they seek support and resources from their current or prospective institutions when pursuing new career opportunities.
{"title":"Institutional Support for the Career Advancement of Women Faculty in Science and Academic Medicine: Successes, Challenges, and Future Directions.","authors":"Zhen Bouman Chen, Elena Aikawa, Mabruka Alfaidi, Kamilah Ali, Cassandra L Clift, Ebru Erbay, Gabrielle Fredman, Delphine Gomez, Ngan F Huang, Hong S Lu, Patricia K Nguyen, Suellen Darc Oliveira, Paula Rodriguez-Miguelez, Gopika SenthilKumar, Hanrui Zhang","doi":"10.1161/ATVBAHA.124.320910","DOIUrl":"10.1161/ATVBAHA.124.320910","url":null,"abstract":"<p><p>Institutional support is crucial for the successful career advancement of all faculty but in particular those who are women. Evolving from the past, in which gender disparities were prevalent in many institutions, recent decades have witnessed significant progress in supporting the career advancement of women faculty in science and academic medicine. However, continued advancement is necessary as previously unrecognized needs and new opportunities for improvement emerge. To identify the needs, opportunities, and potential challenges encountered by women faculty, the Women's Leadership Committee of the Arteriosclerosis, Thrombosis, and Vascular Biology Council developed an initiative termed GROWTH (Generating Resources and Opportunities for Women in Technology and Health). The committee designed a survey questionnaire and interviewed 19 leaders with roles and responsibilities in faculty development from a total of 12 institutions across various regions of the United States. The results were compiled, analyzed, and discussed. Based on our interviews and analyses, we present the current status of these representative institutions in supporting faculty development, highlighting efforts specific to women faculty. Through the experiences, insights, and vision of these leaders, we identified success stories, challenges, and future priorities. Our article provides a primer and a snapshot of institutional efforts to support the advancement of women faculty. Importantly, this article can serve as a reference and resource for academic entities seeking ideas to gauge their commitment level to women faculty and to implement new initiatives. Additionally, this article can provide guidance and strategies for women faculty as they seek support and resources from their current or prospective institutions when pursuing new career opportunities.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-18DOI: 10.1161/ATVBAHA.124.319847
Brett P Ransegnola, Tanyaporn Pattarabanjird, Coleen A McNamara
Atherosclerosis is a chronic inflammatory disease whose progression is fueled by proinflammatory moieties and limited by anti-inflammatory mediators. Whereas oxidative damage and the generation of oxidation-specific epitopes that act as damage-associated molecular patterns are highly inflammatory, IgM antibodies produced by B-1 and marginal zone B cells counteract unrestricted inflammation by neutralizing and encouraging clearance of these proinflammatory signals. In this review, we focus on describing the identities of IgM-producing B cells in both mice and humans, elaborating the mechanisms underlying IgM production, and discussing the potential strategies to augment the production of atheroprotective IgM. In addition, we will discuss promising therapeutic interventions in humans to help tip the scale toward augmentation of IgM production and to provide atheroprotection.
动脉粥样硬化是一种慢性炎症性疾病,其进展受到促炎物质的刺激和抗炎介质的限制。氧化损伤和作为损伤相关分子模式的氧化特异性表位的产生具有高度炎症性,而 B-1 和边缘区 B 细胞产生的 IgM 抗体通过中和并促进清除这些促炎症信号来对抗无限制的炎症。在这篇综述中,我们将重点描述小鼠和人类中产生 IgM 的 B 细胞的特性,阐述产生 IgM 的机制,并讨论增强产生动脉粥样硬化保护性 IgM 的潜在策略。此外,我们还将讨论对人类有前景的治疗干预措施,以帮助增强 IgM 的产生并提供动脉粥样硬化保护。
{"title":"Tipping the Scale: Atheroprotective IgM-Producing B Cells in Atherosclerosis.","authors":"Brett P Ransegnola, Tanyaporn Pattarabanjird, Coleen A McNamara","doi":"10.1161/ATVBAHA.124.319847","DOIUrl":"10.1161/ATVBAHA.124.319847","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory disease whose progression is fueled by proinflammatory moieties and limited by anti-inflammatory mediators. Whereas oxidative damage and the generation of oxidation-specific epitopes that act as damage-associated molecular patterns are highly inflammatory, IgM antibodies produced by B-1 and marginal zone B cells counteract unrestricted inflammation by neutralizing and encouraging clearance of these proinflammatory signals. In this review, we focus on describing the identities of IgM-producing B cells in both mice and humans, elaborating the mechanisms underlying IgM production, and discussing the potential strategies to augment the production of atheroprotective IgM. In addition, we will discuss promising therapeutic interventions in humans to help tip the scale toward augmentation of IgM production and to provide atheroprotection.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-08DOI: 10.1161/ATVBAHA.124.321019
Marco Witkowski, Jennifer Wilcox, Valesha Province, Zeneng Wang, Ina Nemet, W H Wilson Tang, Stanley L Hazen
Background: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined.
Methods: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released.
Results: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4.
Conclusions: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted.
{"title":"Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.","authors":"Marco Witkowski, Jennifer Wilcox, Valesha Province, Zeneng Wang, Ina Nemet, W H Wilson Tang, Stanley L Hazen","doi":"10.1161/ATVBAHA.124.321019","DOIUrl":"10.1161/ATVBAHA.124.321019","url":null,"abstract":"<p><strong>Background: </strong>Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined.</p><p><strong>Methods: </strong>Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released.</p><p><strong>Results: </strong>Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; <i>P</i><0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (<i>P</i><0.0001 for TRAP6 [thrombin activator peptide 6] and <i>P</i>=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; <i>P</i><0.0001 for TRAP6 and <i>P</i>=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4.</p><p><strong>Conclusions: </strong>Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-11DOI: 10.1161/ATVBAHA.124.321008
Haotian Zhang, Nicholas Kafeiti, Kyla Masarik, Sandy Lee, Xiaoxi Yang, Haoyi Zheng, Huichun Zhan
Background: Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN.
Methods: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines.
Results: Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL (myeloproliferative leukemia virus oncogene) suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function.
Conclusions: JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.
{"title":"Decoding Endothelial MPL and JAK2V617F Mutation: Insight Into Cardiovascular Dysfunction in Myeloproliferative Neoplasms.","authors":"Haotian Zhang, Nicholas Kafeiti, Kyla Masarik, Sandy Lee, Xiaoxi Yang, Haoyi Zheng, Huichun Zhan","doi":"10.1161/ATVBAHA.124.321008","DOIUrl":"10.1161/ATVBAHA.124.321008","url":null,"abstract":"<p><strong>Background: </strong>Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN.</p><p><strong>Methods: </strong>We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines.</p><p><strong>Results: </strong>Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL (myeloproliferative leukemia virus oncogene) suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function.</p><p><strong>Conclusions: </strong>JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-21DOI: 10.1161/ATVBAHA.124.320155
Hafid Ait-Oufella, Peter Libby
{"title":"Inflammation and Atherosclerosis: Prospects for Clinical Trials.","authors":"Hafid Ait-Oufella, Peter Libby","doi":"10.1161/ATVBAHA.124.320155","DOIUrl":"10.1161/ATVBAHA.124.320155","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-07-25DOI: 10.1161/ATVBAHA.124.321189
Harvey G Roweth, Isabelle C Becker, Michael W Malloy, Emily M Clarke, Sophie A Munn, Priya L Kumar, Ivan Aivasovsky, Kobe Tray, Alec A Schmaier, Elisabeth M Battinelli
Background: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated.
Methods: Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1Plt KO). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RT-PCR (reverse transcription-polymerase chain reaction). The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry.
Results: Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1Plt KO mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1Plt KO mice had increased tumor cell retention and extravasation. Serum from Angpt1Plt KO mice increased endothelial permeability and reduced VE (vascular endothelial)-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1WT).
Conclusions: Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.
{"title":"Platelet Angiopoietin-1 Protects Against Murine Models of Tumor Metastasis.","authors":"Harvey G Roweth, Isabelle C Becker, Michael W Malloy, Emily M Clarke, Sophie A Munn, Priya L Kumar, Ivan Aivasovsky, Kobe Tray, Alec A Schmaier, Elisabeth M Battinelli","doi":"10.1161/ATVBAHA.124.321189","DOIUrl":"10.1161/ATVBAHA.124.321189","url":null,"abstract":"<p><strong>Background: </strong>In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated.</p><p><strong>Methods: </strong>Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1<sup>Plt KO</sup>). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RT-PCR (reverse transcription-polymerase chain reaction). The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry.</p><p><strong>Results: </strong>Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1<sup>Plt KO</sup> mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1<sup>Plt KO</sup> mice had increased tumor cell retention and extravasation. Serum from Angpt1<sup>Plt KO</sup> mice increased endothelial permeability and reduced VE (vascular endothelial)-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1<sup>WT</sup>).</p><p><strong>Conclusions: </strong>Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-21DOI: 10.1161/ATVBAHA.124.321299
Marta Brambilla, Alessia Becchetti, Kevin Nallio, Marina Camera
{"title":"Letter by Brambilla et al Regarding Article, \"Monocyte-Mediated Thrombosis Linked to Circulating Tissue-Factor and Immune Paralysis in COVID-19\".","authors":"Marta Brambilla, Alessia Becchetti, Kevin Nallio, Marina Camera","doi":"10.1161/ATVBAHA.124.321299","DOIUrl":"https://doi.org/10.1161/ATVBAHA.124.321299","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-01DOI: 10.1161/ATVBAHA.124.321007
Fan Bu, Junhui Wang, Juanjiang Chen, Qi Zhang, Xiaomin Lin, Ruyi Zhang, Huanlan Bai, Yuneng Hua, Haifang Wang, Mei Huang, Yiyi Huang, Yuling Lin, Xiumei Hu, Lei Zheng, Qian Wang
Background: HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 can predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis; however, the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis.
Methods: HCC-1 expression in serum, atherosclerotic plaques, and normal arterial tissue from patients with atherosclerosis and control group was assessed by ELISA, immunohistochemistry and confocal microscope, and bioinformatic analysis. The atherosclerotic model of HCC-1 overexpressing and control mice was generated by tail vein injection of adeno-associated virus serotype 9-HCC-1 on an ApoE-/- background. Cell adhesion, polarization, and pyroptosis were evaluated in vitro. The relationship between HCC-1 concentration in serum and atherosclerosis was analyzed in patients with atherosclerosis.
Results: HCC-1 expression was positively correlated with the occurrence and stable-unstable switch of atherosclerosis under bioinformatic analysis, which is further supported by the results of increased HCC-1 expression in atherosclerosis patients both in serum and atherosclerotic plaque. adeno-associated virus serotype 9-HCC-1 mice had higher levels of inflammatory factors, increased macrophage accumulation and pyroptotic rate in plaque, and decreased atherosclerotic plaque stability. In vitro, HCC-1 promoted monocyte adhesion and M1 polarization and induced inflammation and pyroptosis both in endothelial cells and macrophages.
Conclusions: HCC-1 expression was increased in patients with atherosclerosis, and HCC-1 overexpression accelerated atherosclerotic burden via an enhancement in monocyte recruitment, M1 polarization, and pyroptosis both in endothelial cells and macrophages. Our findings suggested that HCC-1 may serve as an early biomarker for the diagnosis of atherosclerosis, with the capacity to reflect the degree of stenosis.
{"title":"HCC-1 Accelerates Atherosclerosis by Inducing Endothelial Cell and Macrophage Pyroptosis and Serves as an Early Diagnostic Biomarker.","authors":"Fan Bu, Junhui Wang, Juanjiang Chen, Qi Zhang, Xiaomin Lin, Ruyi Zhang, Huanlan Bai, Yuneng Hua, Haifang Wang, Mei Huang, Yiyi Huang, Yuling Lin, Xiumei Hu, Lei Zheng, Qian Wang","doi":"10.1161/ATVBAHA.124.321007","DOIUrl":"10.1161/ATVBAHA.124.321007","url":null,"abstract":"<p><strong>Background: </strong>HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 can predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis; however, the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis.</p><p><strong>Methods: </strong>HCC-1 expression in serum, atherosclerotic plaques, and normal arterial tissue from patients with atherosclerosis and control group was assessed by ELISA, immunohistochemistry and confocal microscope, and bioinformatic analysis. The atherosclerotic model of HCC-1 overexpressing and control mice was generated by tail vein injection of adeno-associated virus serotype 9-HCC-1 on an ApoE<sup>-/-</sup> background. Cell adhesion, polarization, and pyroptosis were evaluated in vitro. The relationship between HCC-1 concentration in serum and atherosclerosis was analyzed in patients with atherosclerosis.</p><p><strong>Results: </strong>HCC-1 expression was positively correlated with the occurrence and stable-unstable switch of atherosclerosis under bioinformatic analysis, which is further supported by the results of increased HCC-1 expression in atherosclerosis patients both in serum and atherosclerotic plaque. adeno-associated virus serotype 9-HCC-1 mice had higher levels of inflammatory factors, increased macrophage accumulation and pyroptotic rate in plaque, and decreased atherosclerotic plaque stability. In vitro, HCC-1 promoted monocyte adhesion and M1 polarization and induced inflammation and pyroptosis both in endothelial cells and macrophages.</p><p><strong>Conclusions: </strong>HCC-1 expression was increased in patients with atherosclerosis, and HCC-1 overexpression accelerated atherosclerotic burden via an enhancement in monocyte recruitment, M1 polarization, and pyroptosis both in endothelial cells and macrophages. Our findings suggested that HCC-1 may serve as an early biomarker for the diagnosis of atherosclerosis, with the capacity to reflect the degree of stenosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-21DOI: 10.1161/ATV.0000000000000176
{"title":"Correction to: Chronic E-Cigarette Use Impairs Endothelial Function on the Physiological and Cellular Levels.","authors":"","doi":"10.1161/ATV.0000000000000176","DOIUrl":"https://doi.org/10.1161/ATV.0000000000000176","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}