Pub Date : 2024-11-09DOI: 10.1016/j.atherosclerosis.2024.119051
Iris M. Harmsen , Frank L.J. Visseren , Madeleine Kok , Pim A. de Jong , Wilko Spiering
Background and aims
Pseudoxanthoma elasticum (PXE) patients have more arterial calcification due to lower levels of inorganic pyrophosphate, caused by mutations in the ABCC6 gene, but the relation with vascular complications is poorly understood. Because of the slow progressing nature of arterial disease in PXE patients, there is a need for a valid and reliable intermediate endpoint to be used in future clinical trials. Arterial calcification measured on computed tomography (CT) is a promising candidate, if associated with future cardiovascular events. We aimed to establish the relation between arterial calcification measured on CT and future cardiovascular events in patients with PXE.
Methods
In this prospective cohort study, patients with PXE from the Dutch UMC Utrecht Expertise Center for PXE (UECP) were included. Arterial calcification volume was measured on low dose full body CT scans. Patient were followed for incident cardiovascular events. The relation between arterial calcification and the risk of cardiovascular events was analyzed using Cox proportional hazard models.
Results
In 326 patients (median follow-up 6.0, IQR 3.8–8.2 years) 41 cardiovascular events were observed (21 events per 1000 person years). In patients with no cardiovascular history, there was a significant relation between the log arterial calcification volume at baseline and future cardiovascular events (adjusted HR: 1.87, 95 % CI: 1.14–3.09, per 1 log unit increase in arterial calcification). There was no relation in patients with clinical manifest cardiovascular disease at baseline between arterial calcification volume and future cardiovascular events.
Conclusions
Higher arterial calcification volumes on CT in PXE patients are associated with a higher risk of a first cardiovascular event. This cohort study suggests that arterial calcification can be used as an intermediate endpoint in studies evaluating interventions to lower the risk of cardiovascular events.
{"title":"Arterial calcification volume is associated with a higher risk of cardiovascular events in pseudoxanthoma elasticum","authors":"Iris M. Harmsen , Frank L.J. Visseren , Madeleine Kok , Pim A. de Jong , Wilko Spiering","doi":"10.1016/j.atherosclerosis.2024.119051","DOIUrl":"10.1016/j.atherosclerosis.2024.119051","url":null,"abstract":"<div><h3>Background and aims</h3><div>Pseudoxanthoma elasticum (PXE) patients have more arterial calcification due to lower levels of inorganic pyrophosphate, caused by mutations in the <em>ABCC6</em> gene, but the relation with vascular complications is poorly understood. Because of the slow progressing nature of arterial disease in PXE patients, there is a need for a valid and reliable intermediate endpoint to be used in future clinical trials. Arterial calcification measured on computed tomography (CT) is a promising candidate, if associated with future cardiovascular events. We aimed to establish the relation between arterial calcification measured on CT and future cardiovascular events in patients with PXE.</div></div><div><h3>Methods</h3><div>In this prospective cohort study, patients with PXE from the Dutch UMC Utrecht Expertise Center for PXE (UECP) were included. Arterial calcification volume was measured on low dose full body CT scans. Patient were followed for incident cardiovascular events. The relation between arterial calcification and the risk of cardiovascular events was analyzed using Cox proportional hazard models.</div></div><div><h3>Results</h3><div>In 326 patients (median follow-up 6.0, IQR 3.8–8.2 years) 41 cardiovascular events were observed (21 events per 1000 person years). In patients with no cardiovascular history, there was a significant relation between the log arterial calcification volume at baseline and future cardiovascular events (adjusted HR: 1.87, 95 % CI: 1.14–3.09, per 1 log unit increase in arterial calcification). There was no relation in patients with clinical manifest cardiovascular disease at baseline between arterial calcification volume and future cardiovascular events.</div></div><div><h3>Conclusions</h3><div>Higher arterial calcification volumes on CT in PXE patients are associated with a higher risk of a first cardiovascular event. This cohort study suggests that arterial calcification can be used as an intermediate endpoint in studies evaluating interventions to lower the risk of cardiovascular events.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119051"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-09DOI: 10.1016/j.atherosclerosis.2024.119052
Hyae Yon Kweon , Eun Ju Song , Se-Jin Jeong , SoonHo Lee , Seong-Keun Sonn , Seungwoon Seo , Jing Jin , Sinai Kim , Tae Kyeong Kim , Shin Hye Moon , Doyeon Kim , Young Mi Park , Hyun Ae Woo , Goo Taeg Oh
Backgroungd and aims
Peroxiredoxin 5 (PRDX5), an atypical 2-Cys peroxiredoxin (PRDX), is known to regulate global oxidative stresses and inflammatory responses. Inflammation and oxidative stress are pivotal factors in the development of atherosclerosis, especially in the context of vascular endothelial dysfunction. However, effects of PRDX5 on atherosclerosis remain unclear. This study aimed to elucidate the role of PRDX5 in the pathogenesis of atherosclerosis.
Methods
For in vivo analysis, normal chow diet 60-week old Apolipoprotein E knockout (ApoE−/−) and Prdx5−/−; ApoE−/− mice were used for the experiments. For in vitro analysis, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized LDL (oxLDL; 50 ng/ml) for 24hrs, following serum starvation by incubation with serum-free Endothelial Cell Growth Medium-2 (EGM-2) for 1hr.
Results
We observed elevated PRDX5 expression under atherosclerotic conditions in both humans and mice. Unexpectedly, Prdx5−/−; ApoE−/− mice exhibited reduced plaque formation, with no discernible difference in aortic hydrogen peroxide (H2O2) levels compared to ApoE−/− mice. Additionally, there was a notable decrease in macrophage accumulation and vascular inflammation in the atherosclerotic aorta of Prdx5−/−; ApoE−/−. In vitro, HUVECs stimulated with oxLDL showed upregulated PRDX5 expression in both lysate and culture medium. Moreover, PRDX5 knockdown in oxLDL-stimulated (oxLDL-siPRDX5) HUVECs significantly reduced the migration and adhesion of human monocytic cells (THP-1) to HUVECs, indicating diminished vascular immune responses. Mechanistically, both in vivo and in vitro, PRDX5 deficiency inhibited the Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (MyD88) signaling pathway, resulting in reduced nuclear factor kappa B (NF-κB) and P38 phosphorylation. Furthermore, treatment with recombinant PRDX5 (rPRDX5) protein restored TLR4/MyD88 signaling in oxLDL-siPRDX5 HUVECs.
Conclusions
These data demonstrate that extracellular PRDX5 contributes to endothelial inflammation, promoting macrophage accumulation in the atherosclerotic aorta through activation of TLR4/MyD88/NF-κB and P38 signaling pathways, thereby exacerbating the progression of atherosclerosis.
{"title":"Extracellular peroxiredoxin 5 exacerbates atherosclerosis via the TLR4/MyD88 pathway","authors":"Hyae Yon Kweon , Eun Ju Song , Se-Jin Jeong , SoonHo Lee , Seong-Keun Sonn , Seungwoon Seo , Jing Jin , Sinai Kim , Tae Kyeong Kim , Shin Hye Moon , Doyeon Kim , Young Mi Park , Hyun Ae Woo , Goo Taeg Oh","doi":"10.1016/j.atherosclerosis.2024.119052","DOIUrl":"10.1016/j.atherosclerosis.2024.119052","url":null,"abstract":"<div><h3>Backgroungd and aims</h3><div>Peroxiredoxin 5 (PRDX5), an atypical 2-Cys peroxiredoxin (PRDX), is known to regulate global oxidative stresses and inflammatory responses. Inflammation and oxidative stress are pivotal factors in the development of atherosclerosis, especially in the context of vascular endothelial dysfunction. However, effects of PRDX5 on atherosclerosis remain unclear. This study aimed to elucidate the role of PRDX5 in the pathogenesis of atherosclerosis.</div></div><div><h3>Methods</h3><div>For <em>in vivo</em> analysis, normal chow diet 60-week old Apolipoprotein E knockout (<em>ApoE</em><sup><em>−/−</em></sup>) and <em>Prdx5</em><sup><em>−/−</em></sup><em>; ApoE</em><sup><em>−/−</em></sup> mice were used for the experiments. For <em>in vitro</em> analysis, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized LDL (oxLDL; 50 ng/ml) for 24hrs, following serum starvation by incubation with serum-free Endothelial Cell Growth Medium-2 (EGM-2) for 1hr.</div></div><div><h3>Results</h3><div>We observed elevated PRDX5 expression under atherosclerotic conditions in both humans and mice. Unexpectedly, <em>Prdx5</em><sup><em>−/−</em></sup><em>; ApoE</em><sup><em>−/−</em></sup> mice exhibited reduced plaque formation, with no discernible difference in aortic hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) levels compared to <em>ApoE</em><sup><em>−/−</em></sup> mice. Additionally, there was a notable decrease in macrophage accumulation and vascular inflammation in the atherosclerotic aorta of <em>Prdx5</em><sup><em>−/−</em></sup><em>; ApoE</em><sup><em>−/−</em></sup>. <em>In vitro,</em> HUVECs stimulated with oxLDL showed upregulated PRDX5 expression in both lysate and culture medium. Moreover, PRDX5 knockdown in oxLDL-stimulated (oxLDL-siPRDX5) HUVECs significantly reduced the migration and adhesion of human monocytic cells (THP-1) to HUVECs, indicating diminished vascular immune responses. Mechanistically, both <em>in vivo</em> and <em>in vitro</em>, PRDX5 deficiency inhibited the Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response 88 (MyD88) signaling pathway, resulting in reduced nuclear factor kappa B (NF-κB) and P38 phosphorylation. Furthermore, treatment with recombinant PRDX5 (rPRDX5) protein restored TLR4/MyD88 signaling in oxLDL-<em>siPRDX5</em> HUVECs.</div></div><div><h3>Conclusions</h3><div>These data demonstrate that extracellular PRDX5 contributes to endothelial inflammation, promoting macrophage accumulation in the atherosclerotic aorta through activation of TLR4/MyD88/NF-κB and P38 signaling pathways, thereby exacerbating the progression of atherosclerosis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"400 ","pages":"Article 119052"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08DOI: 10.1016/j.atherosclerosis.2024.119049
Yoshiyasu Takefuji
{"title":"Unveiling feature importance biases in linear regression: Implications for protein-centric cardiovascular research.","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.atherosclerosis.2024.119049","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2024.119049","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119049"},"PeriodicalIF":4.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1016/j.atherosclerosis.2024.118634
Heinz Drexel, Andreas Festa
{"title":"Reply to: “Correspondence on: “Subclinical atherosclerosis: More data – More insights into prevention” ”","authors":"Heinz Drexel, Andreas Festa","doi":"10.1016/j.atherosclerosis.2024.118634","DOIUrl":"10.1016/j.atherosclerosis.2024.118634","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 118634"},"PeriodicalIF":4.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1016/j.atherosclerosis.2024.119043
Wenyi Nie , Yingbin Yue , Jingqing Hu
{"title":"PCSK9 inhibitors in the management of atherosclerotic cardiovascular disease: Current clinical trials and future directions","authors":"Wenyi Nie , Yingbin Yue , Jingqing Hu","doi":"10.1016/j.atherosclerosis.2024.119043","DOIUrl":"10.1016/j.atherosclerosis.2024.119043","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"399 ","pages":"Article 119043"},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.atherosclerosis.2024.118584
Smriti Sharma , Tyler Artner , Klaus T. Preissner , Irene M. Lang
Cardiovascular diseases (CVD) and their complications continue to be the leading cause of mortality globally. With recent advancements in molecular analytics, individualized treatments are gradually applied to the diagnosis and treatment of CVD. In the field of diagnostics, liquid biopsy combined with modern analytical technologies is the most popular natural source to identify disease biomarkers, as has been successfully demonstrated in the cancer field. While it is not easy to obtain any diseased tissue for different types of CVD such as atherosclerosis, deep vein thrombosis or stroke, liquid biopsies provide a simple and non-invasive alternative to surgical tissue specimens to obtain dynamic molecular information reflecting disease states. The release of cell-free ribonucleic acids (cfRNA) from stressed/damaged/dying and/or necrotic cells is a common physiological phenomenon. CfRNAs are a heterogeneous population of various types of extracellular RNA found in body fluids (blood, urine, saliva, cerebrospinal fluid) or in association with vascular/atherosclerotic tissue, offering insights into disease pathology on a diagnostic front. In particular, cf-ribosomal RNA has been shown to act as a damaging molecule in several cardio-vascular disease conditions. Moreover, such pathophysiological functions of cfRNA in CVD have been successfully antagonized by the administration of RNases. In this review, we discuss the origin, structure, types, and potential utilization of cfRNA in the diagnosis of CVD. Together with the analysis of established CVD biomarkers, the profiling of cfRNA in body fluids may thereby provide a promising approach for early disease detection and monitoring.
{"title":"Nucleic acid liquid biopsies in cardiovascular disease: Cell-free RNA liquid biopsies in cardiovascular disease","authors":"Smriti Sharma , Tyler Artner , Klaus T. Preissner , Irene M. Lang","doi":"10.1016/j.atherosclerosis.2024.118584","DOIUrl":"10.1016/j.atherosclerosis.2024.118584","url":null,"abstract":"<div><div>Cardiovascular diseases (CVD) and their complications continue to be the leading cause of mortality globally. With recent advancements in molecular analytics, individualized treatments are gradually applied to the diagnosis and treatment of CVD. In the field of diagnostics, liquid biopsy combined with modern analytical technologies is the most popular natural source to identify disease biomarkers, as has been successfully demonstrated in the cancer field. While it is not easy to obtain any diseased tissue for different types of CVD such as atherosclerosis, deep vein thrombosis or stroke, liquid biopsies provide a simple and non-invasive alternative to surgical tissue specimens to obtain dynamic molecular information reflecting disease states. The release of cell-free ribonucleic acids (cfRNA) from stressed/damaged/dying and/or necrotic cells is a common physiological phenomenon. CfRNAs are a heterogeneous population of various types of extracellular RNA found in body fluids (blood, urine, saliva, cerebrospinal fluid) or in association with vascular/atherosclerotic tissue, offering insights into disease pathology on a diagnostic front. In particular, cf-ribosomal RNA has been shown to act as a damaging molecule in several cardio-vascular disease conditions. Moreover, such pathophysiological functions of cfRNA in CVD have been successfully antagonized by the administration of RNases. In this review, we discuss the origin, structure, types, and potential utilization of cfRNA in the diagnosis of CVD. Together with the analysis of established CVD biomarkers, the profiling of cfRNA in body fluids may thereby provide a promising approach for early disease detection and monitoring.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118584"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.atherosclerosis.2024.118618
Alexander C. Razavi, Roger S. Blumenthal, Mouaz H. Al-Mallah, Mahmoud Al Rifai
{"title":"Coronary artery calcium density progression: Should we measure it?","authors":"Alexander C. Razavi, Roger S. Blumenthal, Mouaz H. Al-Mallah, Mahmoud Al Rifai","doi":"10.1016/j.atherosclerosis.2024.118618","DOIUrl":"10.1016/j.atherosclerosis.2024.118618","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118618"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.atherosclerosis.2024.117580
Laura Valentina Klüner, Kenneth Chan, Charalambos Antoniades
With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification. New radiotranscriptomic techniques even capture underlying bio-histochemical processes through higher-order structural analysis of voxels on CT images. In the near future, the international large-scale Oxford Risk Factors And Non-invasive Imaging (ORFAN) study will provide a powerful platform for testing and validating prognostic AI-based models. The goal is the transition of these new approaches from research settings into a clinical workflow.
In this review, we present an overview of existing AI-based techniques with focus on imaging biomarkers to determine the degree of coronary inflammation, coronary plaques, and the associated risk. Further, current limitations using AI-based approaches as well as the priorities to address these challenges will be discussed. This will pave the way for an AI-enabled risk assessment tool to detect vulnerable atherosclerotic plaques and to guide treatment strategies for patients.
{"title":"Using artificial intelligence to study atherosclerosis from computed tomography imaging: A state-of-the-art review of the current literature","authors":"Laura Valentina Klüner, Kenneth Chan, Charalambos Antoniades","doi":"10.1016/j.atherosclerosis.2024.117580","DOIUrl":"10.1016/j.atherosclerosis.2024.117580","url":null,"abstract":"<div><div>With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification. New radiotranscriptomic techniques even capture underlying bio-histochemical processes through higher-order structural analysis of voxels on CT images. In the near future, the international large-scale <u>O</u>xford <u>R</u>isk <u>F</u>actors <u>A</u>nd <u>N</u>on-invasive Imaging (ORFAN) study will provide a powerful platform for testing and validating prognostic AI-based models. The goal is the transition of these new approaches from research settings into a clinical workflow.</div><div>In this review, we present an overview of existing AI-based techniques with focus on imaging biomarkers to determine the degree of coronary inflammation, coronary plaques, and the associated risk. Further, current limitations using AI-based approaches as well as the priorities to address these challenges will be discussed. This will pave the way for an AI-enabled risk assessment tool to detect vulnerable atherosclerotic plaques and to guide treatment strategies for patients.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 117580"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141132423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.atherosclerosis.2024.118560
Mary Gonzalez Melo, Arnold von Eckardstein, Jerome Robert
Atherosclerotic cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Atherogenesis is a slow and life-long process characterized by the accumulation of lipoproteins and immune cells within the arterial wall. Atherosclerosis has been successfully modeled in animals: However, there are economic, ethical, and translational concerns when using these models. There is also growing recognition of the need for robust human-based in vitro systems that can faithfully recapitulate key aspects of human atherosclerosis. Such systems may offer advantages in terms of scalability, reproducibility, and ability to manipulate specific variables, thereby facilitating a deeper understanding of disease mechanisms and accelerating the development of targeted therapeutics. Leveraging innovative in vitro platforms holds promise in complementing traditional animal models of atherosclerosis. In the present review, we discuss the advantages and disadvantages of recently developed models of atherosclerosis and propose ideas to be considered when developing future generations of models.
{"title":"Modeling human atherosclerotic lesions in the test tube: Are we there yet?","authors":"Mary Gonzalez Melo, Arnold von Eckardstein, Jerome Robert","doi":"10.1016/j.atherosclerosis.2024.118560","DOIUrl":"10.1016/j.atherosclerosis.2024.118560","url":null,"abstract":"<div><div>Atherosclerotic cardiovascular diseases remain a leading cause of morbidity and mortality worldwide. Atherogenesis is a slow and life-long process characterized by the accumulation of lipoproteins and immune cells within the arterial wall. Atherosclerosis has been successfully modeled in animals: However, there are economic, ethical, and translational concerns when using these models. There is also growing recognition of the need for robust human-based <em>in vitro</em> systems that can faithfully recapitulate key aspects of human atherosclerosis. Such systems may offer advantages in terms of scalability, reproducibility, and ability to manipulate specific variables, thereby facilitating a deeper understanding of disease mechanisms and accelerating the development of targeted therapeutics. Leveraging innovative <em>in vitro</em> platforms holds promise in complementing traditional animal models of atherosclerosis. In the present review, we discuss the advantages and disadvantages of recently developed models of atherosclerosis and propose ideas to be considered when developing future generations of models.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118560"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.atherosclerosis.2024.118529
Nicolas Werschler , Clement Quintard , Stephanie Nguyen , Josef Penninger
Organoids are self-organizing 3D cell culture models that are valuable for studying the mechanisms underlying both development and disease in multiple species, particularly, in humans. These 3D engineered tissues can mimic the structure and function of human organs in vitro. Methods to generate organoids have substantially improved to better resemble, in various ways, their in vivo counterpart. One of the major limitations in current organoid models is the lack of a functional vascular compartment. Here we discuss methodological approaches to generating perfusable blood vessel networks in organoid systems. Inclusion of perfused vascular compartments markedly enhances the physiological relevance of organoid systems and is a critical step in the establishment of next generation, higher-complexity in vitro systems for use in developmental, clinical, and drug-development settings.
{"title":"Engineering next generation vascularized organoids","authors":"Nicolas Werschler , Clement Quintard , Stephanie Nguyen , Josef Penninger","doi":"10.1016/j.atherosclerosis.2024.118529","DOIUrl":"10.1016/j.atherosclerosis.2024.118529","url":null,"abstract":"<div><div>Organoids are self-organizing 3D cell culture models that are valuable for studying the mechanisms underlying both development and disease in multiple species, particularly, in humans. These 3D engineered tissues can mimic the structure and function of human organs <em>in vitro</em>. Methods to generate organoids have substantially improved to better resemble, in various ways, their <em>in vivo</em> counterpart. One of the major limitations in current organoid models is the lack of a functional vascular compartment. Here we discuss methodological approaches to generating perfusable blood vessel networks in organoid systems. Inclusion of perfused vascular compartments markedly enhances the physiological relevance of organoid systems and is a critical step in the establishment of next generation, higher-complexity <em>in vitro</em> systems for use in developmental, clinical, and drug-development settings.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"398 ","pages":"Article 118529"},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}