Cardiovascular PathologyPub Date : 2026-01-01Epub Date: 2025-08-27DOI: 10.1016/j.carpath.2025.107768
Mingyan Zhu , Guixiang Li , Yungui Li , Jinsong Chen
{"title":"Circ_0005372 targets the miR-153-3p/ITGB3 axis to stimulate the PI3K/AKT signaling pathway to facilitate the occurrence and development of congenital heart disease and pulmonary arterial hypertension in children","authors":"Mingyan Zhu , Guixiang Li , Yungui Li , Jinsong Chen","doi":"10.1016/j.carpath.2025.107768","DOIUrl":"10.1016/j.carpath.2025.107768","url":null,"abstract":"<div><h3>Background</h3><div>Congenital heart disease (CHD) is the most common and highest incidence of congenital malformations in newborn infants. Pulmonary arterial hypertension (PAH) is the most serious complication associated with CHD. It is a great threat to the safety and health of newborns.</div></div><div><h3>Methods</h3><div>The expression of circ_0005372, miR-153-3p, and ITGB3 were detected by Real-time quantitative PCR (RT-qPCR) and western blot (WB). MTT and EdU assays were used to evaluate the viability and proliferation of human pulmonary artery smooth muscle cells (HPASMC). Migration and invasion abilities were determined by wound healing and Transwell assays. Pull down and RNA Immunoprecipitation (RIP), and dual luciferase reporter gene assays were used to detect targeting relationships of circ_0005372, miR-153-3p, and ITGB3.</div></div><div><h3>Results</h3><div>Plasma samples from 27 healthy, CHD, and PAH<img>CHD pairs of newborns were collected. Circ_0005372 was highly expressed in PAH<img>CHD patient samples and HPASMCs under hypoxic conditions. Knockdown of circ_0005372 inhibited HPASMCs viability, proliferation, migration, and invasion. Circ_0005372 targeted miR-153-3p and showed a negative correlation. The inhibitory effect of silencing circ_0005372 on the HPASMCs was reversed by miR-153-3p inhibitor. MiR-153-3p negatively regulated ITGB3, and overexpression of ITGB3 abolished the effect of miR-153-3p in hypoxia-treated HPASMCs. Circ_0005372 could regulate the PI3K/AKT signaling pathway through miR-153-3p/ ITGB3.</div></div><div><h3>Conclusion</h3><div>In summary, circ_0005372 mediates the expression of ITG3B via targeting miR-153-3p, thereby stimulating the PI3K/AKT signaling pathway, helping the proliferation, migration, and invasion of HPASMCs and accelerating the deterioration of PAH<img>CHD.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107768"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144943898","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}
Cardiovascular PathologyPub Date : 2026-01-01Epub Date: 2025-09-18DOI: 10.1016/j.carpath.2025.107782
Jan M. Federspiel , Jan-Christian Reil , Peter H. Schmidt , Paul Teping , Frank Ramsthaler , Tanja Schwab , Hans-Joachim Schäfers
{"title":"Aortic valve morphology rather than aortic valve function, aortic dilatation, and age interferes with ascending aortic structural and biomechanical properties","authors":"Jan M. Federspiel , Jan-Christian Reil , Peter H. Schmidt , Paul Teping , Frank Ramsthaler , Tanja Schwab , Hans-Joachim Schäfers","doi":"10.1016/j.carpath.2025.107782","DOIUrl":"10.1016/j.carpath.2025.107782","url":null,"abstract":"<div><div>Aortic valve (AV) malformation and AV malfunction have been linked to aortic wall degeneration. Studies concomitantly assessing AV morphology, AV function, age, ascending aortic dilatation, and aortic biomechanical properties are lacking. This exploratory study aims to close this gap. Surgical samples of the ascending aorta (n=102) were histologically assessed. Based on echocardiographic studies, the elastic modulus (slope stress-strain curve) was calculated. Patient characteristics were collected from the patient charts. Samples obtained during autopsy (n=10) served as reference for the microscopic analysis. The patient characteristics, structural aortic wall changes, and biomechanical wall properties were statistically explored using comparative analyses and a Spearman correlation matrix. Marked medial degeneration was found significantly earlier in life for unicuspid AV morphology compared to bicuspid and tricuspid AV. Significantly fewer lamellar units and thinner aortic walls were found in surgical samples compared to the reference group regardless of AV morphology, AV function, age, and aortic dilatation. Adventitial structural impairment was associated with stiffer aortic walls. Hints were found that AV morphology (rather than AV function, age, and presence/absence of aortic dilatation) affects structural and functional ascending aortic wall properties. Additionally, the observations suggest more advanced aortic degeneration in association with unicuspid AV, underpin the need for non-surgical control samples in surgical pathological studies, and highlight the importance of the adventitial layer for aortic biomechanics.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107782"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102644","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}
Cardiovascular PathologyPub Date : 2026-01-01Epub Date: 2025-10-31DOI: 10.1016/j.carpath.2025.107789
Nora Bacour , Mohammad Zafar , Nicole Kargin , Bulat Zinganshin , Robert Poelmann , Robert J.M. Klautz , John Elefteriades , Nimrat Grewal
{"title":"Aortic wall lamellar structure in phylogeny and in humans: insights from bicuspid and tricuspid aortic valve morphology","authors":"Nora Bacour , Mohammad Zafar , Nicole Kargin , Bulat Zinganshin , Robert Poelmann , Robert J.M. Klautz , John Elefteriades , Nimrat Grewal","doi":"10.1016/j.carpath.2025.107789","DOIUrl":"10.1016/j.carpath.2025.107789","url":null,"abstract":"<div><h3>Objective</h3><div>Despite a voluminous literature on aortopathy, comparatively little attention has been paid to the lamellar architecture of the aortic wall, including the number and distribution of these layers. This study compares the lamellar organization of the developing aorta in individuals with a bicuspid (BAV) versus tricuspid aortic valve (TAV) and includes a literature review on aortic lamellae in mammals and adult humans.</div></div><div><h3>Methods</h3><div>Non-dilated ascending aortic wall samples (<em>n</em> = 83) were analyzed from individuals aged embryonic to 72 years, categorized into six age groups. Additionally, a literature review was carried out on lamellar counts across species.</div></div><div><h3>Results</h3><div>The elastic lamellae in preterm aortas were well-structured with no pathological features. Conversely, adult aortas showed progressive elastic fiber pathology. The number of lamellae increased with age; neonates had the lowest count, peaking in young children, and gradually decreasing in adolescents. Furthermore, compared to TAV patients, BAV patients showed patterns of thinner intimal layers and fewer elastic lamellae. Our literature review showed that the quantity of lamellae in mammals is correlated with both body size and aortic radius, with smaller animals having fewer lamellae. The ascending thoracic aorta in humans had between 45 and 78 elastic lamellae, while the descending and abdominal aortas had fewer layers.</div></div><div><h3>Conclusion</h3><div>The number of elastic lamellae in the aortic wall is influenced by both age and valve morphology. BAV patients had less lamellae than TAV patients, which could contribute to the disparity in clinical outcomes. In older adults, age-related lamellar degeneration likely increases the risk of aortopathy.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"80 ","pages":"Article 107789"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430418","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}
Cardiovascular PathologyPub Date : 2025-11-01Epub Date: 2025-07-29DOI: 10.1016/j.carpath.2025.107760
Sungyeon Jung , Eun Na Kim , Hye In Lee , Hak Jae Kim , Jiwon Koh
{"title":"A case of cardiac undifferentiated pleomorphic sarcoma treated with post-operative radiotherapy followed by heart transplantation","authors":"Sungyeon Jung , Eun Na Kim , Hye In Lee , Hak Jae Kim , Jiwon Koh","doi":"10.1016/j.carpath.2025.107760","DOIUrl":"10.1016/j.carpath.2025.107760","url":null,"abstract":"<div><div>Cardiac undifferentiated pleomorphic sarcomas (UPS) are extremely rare tumors that typically arise in the left atrium. They behave highly aggressively, requiring multimodality treatment when complete surgical resection is not feasible. Nevertheless, there is ongoing debate regarding the efficacy of adjuvant radiation therapy and the associated risk of radiation-induced cardiotoxicity. Pathologically, there is an emerging connection between cardiac UPS and intimal sarcoma of the great vessels, supported by morphological and genetic similarities. Here, we present the case of a 63-year-old woman diagnosed with a large right ventricular UPS. The patient underwent incomplete tumor resection, which was followed by post-operative radiotherapy. After nine months, her cardiac function deteriorated rapidly, and she ultimately ended up requiring heart transplantation. We discuss this case in the context of the existing literature on the diagnosis and treatment of cardiac UPS, focusing on the histopathologic features of the heart after radiotherapy.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107760"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759264","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}
Cardiovascular PathologyPub Date : 2025-11-01Epub Date: 2025-08-15DOI: 10.1016/j.carpath.2025.107765
Gregory A. Fishbein , Stephen D. Preston
{"title":"Revising the histopathologic definition of myocarditis: Birth of the seaport criteria","authors":"Gregory A. Fishbein , Stephen D. Preston","doi":"10.1016/j.carpath.2025.107765","DOIUrl":"10.1016/j.carpath.2025.107765","url":null,"abstract":"","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107765"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871622","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}
Cardiovascular PathologyPub Date : 2025-11-01Epub Date: 2025-08-05DOI: 10.1016/j.carpath.2025.107763
Sarah Parsons, Hans H de Boer
{"title":"The SCVP and AECVP 'Seaport criteria' for lymphocytic myocarditis: Retrospective application to an autopsy cohort.","authors":"Sarah Parsons, Hans H de Boer","doi":"10.1016/j.carpath.2025.107763","DOIUrl":"10.1016/j.carpath.2025.107763","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing lymphocytic myocarditis in non-biopsy specimens remains challenging due to sampling variability, subjective interpretation of histology, and lack of standardized criteria. In 2025, the Society for Cardiovascular Pathology (SCVP) and the Association for European Cardiovascular Pathology (AECVP) proposed the \"Seaport criteria\" to address these limitations.</p><p><strong>Objective: </strong>To assess the practical applicability of the Seaport criteria in a retrospective cohort of forensic autopsy cases with myocardial lymphocytic-predominant inflammation.</p><p><strong>Methods: </strong>Ninety-three autopsy cases with lymphocytic-predominant myocardial inflammation were re-evaluated according to the Seaport criteria. Death in these cases was attributed to myocarditis (n = 45), unascertained causes (n = 34), or drug toxicity (n = 14). We assessed adherence to the recommended technical requirements, reclassified inflammation as diffuse, multifocal, focal myocarditis, or lymphocytic infiltrates of unknown significance (LIUS), and reviewed the original histological descriptions.</p><p><strong>Results: </strong>Most cases (82 %) met the minimum technical sampling standards. Pediatric cases were disproportionately non-compliant with sampling requirements, but not due to insufficient myocardium being sampled. Original histological reporting varied substantially in terminology and detail, with myocyte injury inconsistently reported and a lack of sufficient information for grading under the Seaport criteria. Re-classification resulted in 36 cases of diffuse, 27 multifocal, 2 focal myocarditis, and 28 LIUS. The most common diagnosis in cases given myocarditis as the cause of death was diffuse myocarditis (33/45), whereas LIUS was most frequent in the drug-related and unascertained cohorts. Myocyte injury was sometimes difficult to interpret.</p><p><strong>Conclusions: </strong>The Seaport criteria are feasible to classify lymphocytic myocarditis in autopsy hearts, with potential to standardize histological assessment and therefore improve diagnostic consistency. However, challenges remain in recognizing myocyte injury. Further prospective multicenter validation is recommended.</p>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":" ","pages":"107763"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793559","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}
Cardiovascular PathologyPub Date : 2025-11-01Epub Date: 2025-07-10DOI: 10.1016/j.carpath.2025.107749
Marisa Prasanpanich , Majid Husain , Nancy J. Halnon , Richard Chang , Neda Zadeh , Jason Knight , Gregory A. Fishbein
{"title":"Cardiac pathology in a patient with a novel pathogenic variant c.703del (p.Ile235SerfsTer4) of the TAFAZZIN gene","authors":"Marisa Prasanpanich , Majid Husain , Nancy J. Halnon , Richard Chang , Neda Zadeh , Jason Knight , Gregory A. Fishbein","doi":"10.1016/j.carpath.2025.107749","DOIUrl":"10.1016/j.carpath.2025.107749","url":null,"abstract":"<div><h3>Introduction</h3><div>Barth syndrome is a mitochondrial disease caused by loss-of-function mutations in the <em>TAFAZZIN</em> gene located on chromosome Xq28 encoding a transacylase essential for cardiolipin remodeling. Most patients develop dilated cardiomyopathy and progressive heart failure within the first year of life with some requiring cardiac transplantation.</div></div><div><h3>Case Report</h3><div>A full-term male infant with an anatomically normal heart presented postnatally with cardiogenic shock necessitating VA-ECMO within the second day of life. WGS revealed a pathogenic c.703del (p.Ile235SerfsTer4) variant in the <em>TAFAZZIN</em> gene. While on the waitlist for cardiac transplantation, he was treated with intravenous Elamipretide, a mitochondrially-targeted tetrapeptide interacting with cardiolipin, without significant side effects, started at three weeks old and continued through transplantation. He underwent a successful orthotopic cardiac transplantation at five months of age. The explanted heart showed dilated left ventricle with hypertrabeculation and was remarkable for endocardial fibroelastosis and diffuse sarcoplasmic vacuolization with coarse granularity. Ultrastructurally, mitochondria displayed megaconia and replacement of cristae by circular, vesicular, cylindrical, and fingerprint-like structures. He continues to do well as an outpatient and remains on subcutaneous Elamipretide.</div></div><div><h3>Summary</h3><div>We describe a case of Barth syndrome harboring a novel pathogenic variant of the <em>TAFAZZIN</em> gene exhibiting dilated cardiomyopathy, hypertrabeculation, endocardial fibroelastosis, and prominent mitochondrial abnormality. Elamipretide was well tolerated.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107749"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616326","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}
{"title":"Anatomical variations of the mitral leaflets: Unified and accessory scallops","authors":"Buse Naz ÇANDIR GÜRSES , Kader YILAR , Çağla ERGİN , Özcan GAYRETLİ","doi":"10.1016/j.carpath.2025.107767","DOIUrl":"10.1016/j.carpath.2025.107767","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate the morphological variants of the leaflets and scallops of the mitral valve in fresh hearts of healthy individuals and to determine their morphometric values.</div></div><div><h3>Methods</h3><div>The hearts of 100 autopsy cases were analysed. The weight and dimensions of the heart and mitral valve circumference were measured. The morphology of the mitral leaflets and scallops and their hinge distances and heights were recorded.</div></div><div><h3>Results</h3><div>In 64 cases, classical leaflet morphology (aortic leaflet, mural leaflet consisting of 3 scallops, superolateral and inferoseptal commissures) was observed. In 24 cases accessory scallops and in 12 cases unified scallops were identified. The mean hinge distance and height of accessory scallops were 8.69±2.5 mm, and 9.79±2.5 mm respectively, and these values were 45.73±9.8 mm, and 11.95±2.3 mm in unified scallops, respectively. Accessory and unified scallops can be found in any region of mural leaflet, but the vast majority (96 %) are associated with it and more than half (60 %) are located at the commissural ends. In 1 case aortic leaflet consisted of two scallops and mural leaflet had 3 scallops in 63 %, 4 scallops in 22 %, 2 scallops in 8 %, 1 scallop in 4 % and 5 scallops in 3 %.</div></div><div><h3>Conclusion</h3><div>Significant morphological variations between mitral leaflets and scallops have been reported. These variations may affect the placement of the suture or device in mitral valve repair. It was also concluded that these variations cannot be predicted by age, gender or cardiac morphometry.</div></div>","PeriodicalId":9451,"journal":{"name":"Cardiovascular Pathology","volume":"79 ","pages":"Article 107767"},"PeriodicalIF":1.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917889","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}