Pub Date : 2025-09-01Epub Date: 2025-05-29DOI: 10.1016/j.carpath.2025.107744
Paavo Immonen , Pranita Zare , Ari Mennander , Timo Paavonen , Pradeep Vaideeswar , Ivana Kholová
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) create a global burden in the field of cardiovascular medicine due to significant morbidity and mortality, particularly in low- and middle-income countries and the underprivileged population.
Sequential surgical specimens of mitral valves excised from 19 patients with moderate to marked rheumatic mitral stenosis were included in this study and compared to eight sequential surgical myxomatous degenerative valves (control). The study group population had a mean age of 43.8 (± standard deviation (SD) 13.3) years and comprised 10 female and nine male patients. The controls included three female and five male patients with a mean age of 61.5 (± SD 16.1) years.
In RHD, the lymphatic vessel size and count per mm² were increased compared to the degenerative valves. Statistical significance was found in the blood and lymphatic vessel size, and lymphatic vessel count. In RHD, the combined blood and lymphatic vessel size increased from 1.45µm² (± SD 2.52) to 4.91 µm² (± SD 6.33). The lymphatic vessel count was 1,123.86 per mm² (± SD 2,154.68) in the RHD and 213.08 per mm² (± SD 390.13) in the myxomatous degenerative valves. Angiogenesis and lymphangiogenesis characterize mitral valves in RHD.
{"title":"Increased angiogenesis and lymphangiogenesis in rheumatic mitral valves","authors":"Paavo Immonen , Pranita Zare , Ari Mennander , Timo Paavonen , Pradeep Vaideeswar , Ivana Kholová","doi":"10.1016/j.carpath.2025.107744","DOIUrl":"10.1016/j.carpath.2025.107744","url":null,"abstract":"<div><div>Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) create a global burden in the field of cardiovascular medicine due to significant morbidity and mortality, particularly in low- and middle-income countries and the underprivileged population.</div><div>Sequential surgical specimens of mitral valves excised from 19 patients with moderate to marked rheumatic mitral stenosis were included in this study and compared to eight sequential surgical myxomatous degenerative valves (control). The study group population had a mean age of 43.8 (± standard deviation (SD) 13.3) years and comprised 10 female and nine male patients. The controls included three female and five male patients with a mean age of 61.5 (± SD 16.1) years.</div><div>In RHD, the lymphatic vessel size and count per mm² were increased compared to the degenerative valves. Statistical significance was found in the blood and lymphatic vessel size, and lymphatic vessel count. In RHD, the combined blood and lymphatic vessel size increased from 1.45µm² (± SD 2.52) to 4.91 µm² (± SD 6.33). The lymphatic vessel count was 1,123.86 per mm² (± SD 2,154.68) in the RHD and 213.08 per mm² (± SD 390.13) in the myxomatous degenerative valves. Angiogenesis and lymphangiogenesis characterize mitral valves in RHD.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107744"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-06-13DOI: 10.1016/j.carpath.2025.107745
Ilyse Darwish , Benoît de Varennes , Pierre Olivier Fiset , Sophie Camilleri-Broët , Vynka Lash , Marcelo Cantarovich , Todd C. Lee , Cecilia T. Costiniuk
A 43-year-old female with a renal transplant presented with fatigue, dyspnea, anemia, and thrombocytopenia. Chest CT revealed pulmonary nodules, and transthoracic echocardiography identified a large, multi-lobulated, multi-cystic mass attached to the pulmonic valve. Pathology demonstrated fungal hyphae, and bronchoalveolar lavage (BAL) fluid grew Aspergillus fumigatus, with a serum Aspergillus galactomannan (GM) antigen index of 1.95. The pulmonic valve was excised and a bioprosthetic valve was inserted. The patient was treated with voriconazole. Pulmonic valve Aspergillus endocarditis (AE) is a rare condition associated with high mortality. Given the rising number of transplant recipients, heightened clinical vigilance is warranted in this population.
{"title":"A renal transplant recipient with a pulmonic valve mass","authors":"Ilyse Darwish , Benoît de Varennes , Pierre Olivier Fiset , Sophie Camilleri-Broët , Vynka Lash , Marcelo Cantarovich , Todd C. Lee , Cecilia T. Costiniuk","doi":"10.1016/j.carpath.2025.107745","DOIUrl":"10.1016/j.carpath.2025.107745","url":null,"abstract":"<div><div>A 43-year-old female with a renal transplant presented with fatigue, dyspnea, anemia, and thrombocytopenia. Chest CT revealed pulmonary nodules, and transthoracic echocardiography identified a large, multi-lobulated, multi-cystic mass attached to the pulmonic valve. Pathology demonstrated fungal hyphae, and bronchoalveolar lavage (BAL) fluid grew <em>Aspergillus fumigatus</em>, with a serum Aspergillus galactomannan (GM) antigen index of 1.95. The pulmonic valve was excised and a bioprosthetic valve was inserted. The patient was treated with voriconazole. Pulmonic valve <em>Aspergillus</em> endocarditis (AE) is a rare condition associated with high mortality. Given the rising number of transplant recipients, heightened clinical vigilance is warranted in this population.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107745"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-07-23DOI: 10.1016/j.carpath.2025.107759
Marc K. Halushka , Giulia d’Amati , Melanie C. Bois , John T. Fallon , Carla Giordano , Karin Klingel , Charles Leduc , Richard N. Mitchell , Stefania Rizzo , Cristina Basso
Background and aim
Lymphocytic myocarditis has long been appreciated as a lymphocyte-predominant myocardial inflammation with resultant myocyte injury. However, current methods of diagnosis on endomyocardial biopsy (EMB) lead to inconsistent diagnoses. To improve patient care, the criteria for the diagnosis of lymphocytic myocarditis on endomyocardial biopsies have been revised to address shortcomings of the Dallas Criteria and European Society of Cardiology (ESC) criteria.
Methods and results
In the Seaport area of Boston, a panel of expert cardiovascular pathologists from the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) completed a three-year project to develop consensus terms and definitions. These “Seaport” criteria for EMB were developed to utilize CD3 immunohistochemistry for T lymphocytes and accurately define each level of histopathologic severity based on extent of infiltrate and presence of myocyte injury. These criteria create a diagnostic approach to lymphocytic myocarditis using three grades of severity (mild, moderate, and severe) along with a category of scattered increased T lymphocytes of undetermined significance (SITUS). The document discusses the role of ancillary studies, the relationship to other diagnostic modalities, and areas of continuing controversy in the development of these criteria.
Conclusion
These consensus-based criteria offer a standardized framework for diagnosing lymphocytic myocarditis in EMB. Adoption of these easy-to-use criteria will improve classification of lymphocytic myocarditis as an aid to diagnose and treat patients.
{"title":"Lymphocytic myocarditis: A histopathologic definition and classification from the Society for Cardiovascular Pathology and Association for European Cardiovascular Pathology. I: Endomyocardial biopsy","authors":"Marc K. Halushka , Giulia d’Amati , Melanie C. Bois , John T. Fallon , Carla Giordano , Karin Klingel , Charles Leduc , Richard N. Mitchell , Stefania Rizzo , Cristina Basso","doi":"10.1016/j.carpath.2025.107759","DOIUrl":"10.1016/j.carpath.2025.107759","url":null,"abstract":"<div><h3>Background and aim</h3><div>Lymphocytic myocarditis has long been appreciated as a lymphocyte-predominant myocardial inflammation with resultant myocyte injury. However, current methods of diagnosis on endomyocardial biopsy (EMB) lead to inconsistent diagnoses. To improve patient care, the criteria for the diagnosis of lymphocytic myocarditis on endomyocardial biopsies have been revised to address shortcomings of the Dallas Criteria and European Society of Cardiology (ESC) criteria.</div></div><div><h3>Methods and results</h3><div>In the Seaport area of Boston, a panel of expert cardiovascular pathologists from the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) completed a three-year project to develop consensus terms and definitions. These “Seaport” criteria for EMB were developed to utilize CD3 immunohistochemistry for T lymphocytes and accurately define each level of histopathologic severity based on extent of infiltrate and presence of myocyte injury. These criteria create a diagnostic approach to lymphocytic myocarditis using three grades of severity (mild, moderate, and severe) along with a category of scattered increased T lymphocytes of undetermined significance (SITUS). The document discusses the role of ancillary studies, the relationship to other diagnostic modalities, and areas of continuing controversy in the development of these criteria.</div></div><div><h3>Conclusion</h3><div>These consensus-based criteria offer a standardized framework for diagnosing lymphocytic myocarditis in EMB. Adoption of these easy-to-use criteria will improve classification of lymphocytic myocarditis as an aid to diagnose and treat patients.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107759"},"PeriodicalIF":1.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As endovascular therapy for ischemic stroke has advanced, we are getting increasing opportunities to study cerebral thromboemboli histologically. These opportunities have not been fully exploited, but some reports suggest that thromboemboli retrieved from cancer patients with stroke are platelet-richer than those from non-cancer patients. Nonbacterial thrombotic endocarditis (NBTE) is an important cause of ischemic stroke in cancer patients. In this study, we analyzed 20 autopsy cases of NBTE (13 of which had advanced cancer), along with cases of cerebral embolism associated with atrial fibrillation (AF, n = 11) and infective endocarditis (IE, n = 7). The histological features of NBTE vegetations (n = 20) were fairly consistent among cases: they were overwhelmingly platelet-dominant and spatially homogeneous, containing few erythrocytes or inflammatory cells. They were little organized, if at all, and were not associated with valvular destruction. Cerebral emboli associated with NBTE (n = 7) were also platelet-dominant. Intracardiac thrombi/vegetations and cerebral emboli associated with AF and IE, in contrast, contained variable amounts of platelets and erythrocytes. NBTE vegetations/emboli, compared with AF thrombi/emboli, had significantly higher %platelet area (intracardiac vegetations/thrombi: 70 ± 15 % vs 33 ± 20 %, p < 0.001; cerebral emboli: 65 ± 16 % vs 25 ± 22 %, p < 0.001) and lower %erythrocyte area (vegetations/thrombi: 9 ± 7 % vs 61 ± 21 %, p < 0.001; emboli: 20 ± 11 % vs 70 ± 9 %, p < 0.001). These results suggest that some platelet-rich thrombi retrieved during mechanical thrombectomy for ischemic stroke in cancer patients are likely to have originated from NBTE. Clinical diagnosis of NBTE is often difficult, but histological analysis of retrieved thrombi may help identify this underdiagnosed condition.
随着缺血性脑卒中血管内治疗的发展,我们对脑血栓栓塞的组织学研究机会越来越多。这些机会尚未得到充分利用,但一些报告表明,从癌症患者卒中中取出的血栓栓子比非癌症患者的血小板更丰富。非细菌性血栓性心内膜炎(NBTE)是癌症患者缺血性脑卒中的重要病因。在这项研究中,我们分析了20例NBTE尸检病例(其中13例为晚期癌症),以及脑栓塞合并心房颤动(AF, n=11)和感染性心内膜炎(IE, n=7)。NBTE植被(n=20)的组织学特征在病例中相当一致:它们绝大多数以血小板为主,空间均匀,含有少量红细胞或炎症细胞。它们几乎没有组织,如果有的话,也与瓣膜破坏无关。NBTE相关脑栓塞(n=7)也以血小板为主。相比之下,AF和IE相关的心内血栓/植被和脑栓塞含有不同数量的血小板和红细胞。NBTE植被/栓塞与房颤血栓/栓塞相比,血小板面积明显更高(心内植被/血栓:70±15% vs 33±20%,p
{"title":"Vegetations and cerebral emboli of non-bacterial thrombotic endocarditis are overwhelmingly platelet-dominant: A possible histological clue for the diagnosis from an autopsy study","authors":"Tomoyuki Otani , Chiyoko Terada-Ikeda , Junpei Koge , Hisao Shimizu , Manabu Matsumoto , Kisaki Amemiya , Yoshihiko Ikeda , Keiko Ohta-Ogo , Emi Date , Norishige Iizuka , Akihiko Yoshizawa , Kinta Hatakeyama","doi":"10.1016/j.carpath.2025.107746","DOIUrl":"10.1016/j.carpath.2025.107746","url":null,"abstract":"<div><div>As endovascular therapy for ischemic stroke has advanced, we are getting increasing opportunities to study cerebral thromboemboli histologically. These opportunities have not been fully exploited, but some reports suggest that thromboemboli retrieved from cancer patients with stroke are platelet-richer than those from non-cancer patients. Nonbacterial thrombotic endocarditis (NBTE) is an important cause of ischemic stroke in cancer patients. In this study, we analyzed 20 autopsy cases of NBTE (13 of which had advanced cancer), along with cases of cerebral embolism associated with atrial fibrillation (AF, <em>n</em> = 11) and infective endocarditis (IE, <em>n</em> = 7). The histological features of NBTE vegetations (<em>n</em> = 20) were fairly consistent among cases: they were overwhelmingly platelet-dominant and spatially homogeneous, containing few erythrocytes or inflammatory cells. They were little organized, if at all, and were not associated with valvular destruction. Cerebral emboli associated with NBTE (<em>n</em> = 7) were also platelet-dominant. Intracardiac thrombi/vegetations and cerebral emboli associated with AF and IE, in contrast, contained variable amounts of platelets and erythrocytes. NBTE vegetations/emboli, compared with AF thrombi/emboli, had significantly higher %platelet area (intracardiac vegetations/thrombi: 70 ± 15 % vs 33 ± 20 %, <em>p</em> < 0.001; cerebral emboli: 65 ± 16 % vs 25 ± 22 %, <em>p</em> < 0.001) and lower %erythrocyte area (vegetations/thrombi: 9 ± 7 % vs 61 ± 21 %, <em>p</em> < 0.001; emboli: 20 ± 11 % vs 70 ± 9 %, <em>p</em> < 0.001). These results suggest that some platelet-rich thrombi retrieved during mechanical thrombectomy for ischemic stroke in cancer patients are likely to have originated from NBTE. Clinical diagnosis of NBTE is often difficult, but histological analysis of retrieved thrombi may help identify this underdiagnosed condition.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107746"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-06-27DOI: 10.1016/j.carpath.2025.107748
Joseph J. Maleszewski , Jytte Banner , Hans de Boer , Monica De Gaspari , Michael C. Fishbein , Sarah Parsons , Barbara Sampson , Mary N. Sheppard , Allard C. Van der Wal , James R. Stone , Katarzyna Michaud
Background and aim
Lymphocytic myocarditis, characterized by lymphocyte-predominant myocardial inflammation with associated myocyte injury, is a term that has decades-old histopathologic criteria when encountered on endomyocardial biopsy. However, the interpretation of non-biopsy specimens such as surgical resections and autopsy samples has lacked standardized histopathologic criteria, despite their growing clinical and forensic relevance. The aim was to develop and establish criteria for the diagnosis and classification of lymphocytic myocarditis in non-biopsy ventricular myocardial specimens.
Methods and results
An international panel of cardiovascular pathologists representing the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) developed a new classification system, which was completed at a final meeting in the Seaport area of Boston. These “Seaport” criteria for non-biopsy specimens formally define lymphocytic myocarditis as myocardial inflammation predominantly composed of lymphocytes, accompanied by myocyte injury not attributable to other causes. Recommendations address specimen type, technical handling, diagnostic thresholds, and qualifiers of chronicity. Diagnostic categories include active myocarditis and lymphocytic infiltrate of uncertain significance (LIUS). The document also outlines the interpretive challenges in attributing causality in autopsy settings, provides guidance on the use of ancillary techniques, and highlights the limitations of current histopathologic approaches.
Conclusion
These consensus-based criteria offer a standardized framework for diagnosing lymphocytic myocarditis in non-biopsy specimens. Adoption of these guidelines is expected to improve diagnostic consistency, enhance research comparability, and inform clinical and forensic evaluations. Future efforts should aim to refine definitions of myocyte injury, validate ancillary techniques, and elucidate the clinical significance of inflammation in the absence of injury.
{"title":"Lymphocytic myocarditis: A histopathologic definition and classification from the society for cardiovascular pathology and association for European cardiovascular pathology. II: Surgical and autopsy specimens","authors":"Joseph J. Maleszewski , Jytte Banner , Hans de Boer , Monica De Gaspari , Michael C. Fishbein , Sarah Parsons , Barbara Sampson , Mary N. Sheppard , Allard C. Van der Wal , James R. Stone , Katarzyna Michaud","doi":"10.1016/j.carpath.2025.107748","DOIUrl":"10.1016/j.carpath.2025.107748","url":null,"abstract":"<div><h3>Background and aim</h3><div>Lymphocytic myocarditis, characterized by lymphocyte-predominant myocardial inflammation with associated myocyte injury, is a term that has decades-old histopathologic criteria when encountered on endomyocardial biopsy. However, the interpretation of non-biopsy specimens such as surgical resections and autopsy samples has lacked standardized histopathologic criteria, despite their growing clinical and forensic relevance. The aim was to develop and establish criteria for the diagnosis and classification of lymphocytic myocarditis in non-biopsy ventricular myocardial specimens.</div></div><div><h3>Methods and results</h3><div>An international panel of cardiovascular pathologists representing the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) developed a new classification system, which was completed at a final meeting in the Seaport area of Boston. These “Seaport” criteria for non-biopsy specimens formally define lymphocytic myocarditis as myocardial inflammation predominantly composed of lymphocytes, accompanied by myocyte injury not attributable to other causes. Recommendations address specimen type, technical handling, diagnostic thresholds, and qualifiers of chronicity. Diagnostic categories include active myocarditis and lymphocytic infiltrate of uncertain significance (LIUS). The document also outlines the interpretive challenges in attributing causality in autopsy settings, provides guidance on the use of ancillary techniques, and highlights the limitations of current histopathologic approaches.</div></div><div><h3>Conclusion</h3><div>These consensus-based criteria offer a standardized framework for diagnosing lymphocytic myocarditis in non-biopsy specimens. Adoption of these guidelines is expected to improve diagnostic consistency, enhance research comparability, and inform clinical and forensic evaluations. Future efforts should aim to refine definitions of myocyte injury, validate ancillary techniques, and elucidate the clinical significance of inflammation in the absence of injury.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107748"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-05-10DOI: 10.1016/j.carpath.2025.107742
Jing Wang , Yahui Zhang , Caixing Cao , Jiale Hua , Li Xing , Changxin Wu
Regulating the differentiation of monocytes into M2 macrophages can promote the regression of Atherosclerosis (AS) plaque. However, the key molecules regulating the differentiation of monocytes to M2 are unknown. In this study, we reported that adenosine-activated protein kinase α1 (AMPKα1) plays an anti-AS role by polarizing monocytes to an M2 phenotype via promoting fatty acid oxidation (FAO). AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to provide fatty acids for FAO. Furthermore, AMPKα1 can induce lysosomal biogenesis and enhance lipolysis by promoting the transcription factor EB (TFEB) expression and facilitating TFEB nuclear translocation. In conclusion, AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to produce fatty acids, which may represent a mechanism to promote FAO and inflammatory monocytes differentiation towards M2 phenotype.
{"title":"The anti-atherosclerosis effect and molecular mechanism of AMPKα1 by polarizing monocytes to an M2 phenotype via cell-intrinsic lysosomal lipolysis","authors":"Jing Wang , Yahui Zhang , Caixing Cao , Jiale Hua , Li Xing , Changxin Wu","doi":"10.1016/j.carpath.2025.107742","DOIUrl":"10.1016/j.carpath.2025.107742","url":null,"abstract":"<div><div>Regulating the differentiation of monocytes into M2 macrophages can promote the regression of Atherosclerosis (AS) plaque. However, the key molecules regulating the differentiation of monocytes to M2 are unknown. In this study, we reported that adenosine-activated protein kinase α1 (AMPKα1) plays an anti-AS role by polarizing monocytes to an M2 phenotype via promoting fatty acid oxidation (FAO). AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to provide fatty acids for FAO. Furthermore, AMPKα1 can induce lysosomal biogenesis and enhance lipolysis by promoting the transcription factor EB (TFEB) expression and facilitating TFEB nuclear translocation. In conclusion, AMPKα1 enhances the decomposition of cholesterol esters by increasing lysosomal acid lipase expression to produce fatty acids, which may represent a mechanism to promote FAO and inflammatory monocytes differentiation towards M2 phenotype.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107742"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arrhythmogenic cardiomyopathy (ACM) is a myocardial disorder characterized by arrhythmias and an increased risk of sudden cardiac death, particularly in left-dominant arrhythmogenic cardiomyopathy (LACM), which primarily affects the left ventricle. This study aims to elucidate the cellular and molecular mechanisms underlying LACM by performing an in-depth single-nucleus RNA sequencing (snRNA-seq) analysis to identify key transcriptional signatures and pathways involved in the disease's pathogenesis.
Method
Human heart samples were collected from five patients undergoing heart transplantation due to ACM and from four healthy donors. Single nuclei were isolated from myocardial tissues and subjected to snRNA-seq using the 10 × Genomics Chromium platform. Data were processed and analyzed to identify distinct cell populations and their differentially expressed genes. Immunofluorescence staining was used to validate key findings.
Result
The snRNA-seq analysis revealed an increased proportion of fibroblasts and adipocytes in the left ventricles of LACM patients, suggesting a cellular basis for the fibrofatty remodeling observed in the disease. Key cell populations, including cardiomyocytes (CMs), fibroblasts (Fbs), and adipocytes (Adipo), were identified with distinct transcriptional profiles. We identified a disease-associated cardiomyocyte subpopulation (CM1) characterized by upregulation of fibrosis-, metabolism-, and stress-related markers, indicating transcriptional remodeling processes involved in LACM. The Fb subgroup Fb1 was characterized by genes involved in the PI3K-AKT signaling pathway. Adipocyte subpopulations exhibited gene expression features reflecting adaptation to the cardiac pathological environment, including markers associated with extracellular matrix remodeling and metabolic stress.
Immunofluorescence staining validated the high expression of key markers of LACM patients.
Conclusion
This study provides a cellular and molecular characterization of LACM, identifying key pathways and transcriptional signatures that contribute to the disease's pathogenesis. These findings enhance our understanding of LACM and offer potential targets for therapeutic intervention.
{"title":"Molecular features and cell composition of left-dominant arrhythmogenic cardiomyopathy reveals key pathways and therapeutic targets","authors":"Yiqi Zhao , Mengda Xu , Xiumeng Hua , Yuan Chang , Yixuan Sheng , Dan Shan , Ningning Zhang , Xiao Chen , Jiangping Song","doi":"10.1016/j.carpath.2025.107743","DOIUrl":"10.1016/j.carpath.2025.107743","url":null,"abstract":"<div><h3>Background</h3><div>Arrhythmogenic cardiomyopathy (ACM) is a myocardial disorder characterized by arrhythmias and an increased risk of sudden cardiac death, particularly in left-dominant arrhythmogenic cardiomyopathy (LACM), which primarily affects the left ventricle. This study aims to elucidate the cellular and molecular mechanisms underlying LACM by performing an in-depth single-nucleus RNA sequencing (snRNA-seq) analysis to identify key transcriptional signatures and pathways involved in the disease's pathogenesis.</div></div><div><h3>Method</h3><div>Human heart samples were collected from five patients undergoing heart transplantation due to ACM and from four healthy donors. Single nuclei were isolated from myocardial tissues and subjected to snRNA-seq using the 10 × Genomics Chromium platform. Data were processed and analyzed to identify distinct cell populations and their differentially expressed genes. Immunofluorescence staining was used to validate key findings.</div></div><div><h3>Result</h3><div>The snRNA-seq analysis revealed an increased proportion of fibroblasts and adipocytes in the left ventricles of LACM patients, suggesting a cellular basis for the fibrofatty remodeling observed in the disease. Key cell populations, including cardiomyocytes (CMs), fibroblasts (Fbs), and adipocytes (Adipo), were identified with distinct transcriptional profiles. We identified a disease-associated cardiomyocyte subpopulation (CM1) characterized by upregulation of fibrosis-, metabolism-, and stress-related markers, indicating transcriptional remodeling processes involved in LACM. The Fb subgroup Fb1 was characterized by genes involved in the PI3K-AKT signaling pathway. Adipocyte subpopulations exhibited gene expression features reflecting adaptation to the cardiac pathological environment, including markers associated with extracellular matrix remodeling and metabolic stress.</div><div>Immunofluorescence staining validated the high expression of key markers of LACM patients.</div></div><div><h3>Conclusion</h3><div>This study provides a cellular and molecular characterization of LACM, identifying key pathways and transcriptional signatures that contribute to the disease's pathogenesis. These findings enhance our understanding of LACM and offer potential targets for therapeutic intervention.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107743"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-06-22DOI: 10.1016/j.carpath.2025.107747
Petr Handlos , Klára Handlosová , Vladimír Židlík , Vladimíra Gebauerová , Matěj Uvíra
This paper presents a fatal case of a 31-year-old female intravenous amphetamine user in the late stage of pregnancy who suffered a sudden collapse at home. The autopsy revealed hemopericardium resulting from an aorto-pericardial fistula. Histological examination of the aortic valve revealed multiple abscesses. Moreover, the histological examination also proved the presence of foreign bodies in the fistula and a granulomatous reaction with numerous multinucleated giant cells surrounding the bodies in the wall of the aorto-pericardial fistula necrosis as well as purulent phlegmonous inflammation. The foreign bodies were positive for amphetamine and methamphetamine. These findings suggest that the aorto-pericardial fistula developed due to intravenous drug abuse.
{"title":"Aorto-pericardial fistula in an intravenous drug addict with infective endocarditis of the aortic valve","authors":"Petr Handlos , Klára Handlosová , Vladimír Židlík , Vladimíra Gebauerová , Matěj Uvíra","doi":"10.1016/j.carpath.2025.107747","DOIUrl":"10.1016/j.carpath.2025.107747","url":null,"abstract":"<div><div>This paper presents a fatal case of a 31-year-old female intravenous amphetamine user in the late stage of pregnancy who suffered a sudden collapse at home. The autopsy revealed hemopericardium resulting from an aorto-pericardial fistula. Histological examination of the aortic valve revealed multiple abscesses. Moreover, the histological examination also proved the presence of foreign bodies in the fistula and a granulomatous reaction with numerous multinucleated giant cells surrounding the bodies in the wall of the aorto-pericardial fistula necrosis as well as purulent phlegmonous inflammation. The foreign bodies were positive for amphetamine and methamphetamine. These findings suggest that the aorto-pericardial fistula developed due to intravenous drug abuse.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"78 ","pages":"Article 107747"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}