Cardiovascular Pathology最新文献_第2页

Regional and temporal changes in early structural remodeling following myocardial infarction via semi-automatic image analysis 通过半自动图像分析心肌梗死后早期结构重构的区域和时间变化。

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-22 DOI: 10.1016/j.carpath.2025.107801

Catherine C. Eberman , Yuming Liu , Kevin W. Eliceiri , Colleen M. Witzenburg

Reperfusion therapy, the restoration of blood flow following myocardial infarction, is one of the most effective treatment strategies. Unlike early reperfusion, late reperfusion therapy (LRT) has not been linked to differences in infarct size or collagen density. To evaluate the spatial-temporal effects of LRT, we conducted multimodal imaging of histologic sections of rat myocardium following permanent coronary artery occlusion or three hours of occlusion. Semi-automatic partitioning identified the infarct core, border, and peripheral regions from label-free liquid crystal based polarized light microscopy (PolScope) images taken over 5 days of healing. Brightfield and standard polarized light microscopy images of hematoxylin-eosin or Picrosirius Red stained sections were used to determine cellular and collagen fiber densities, respectively. Even when we consider multiple definitions for the vulnerable infarct border, its size decreased faster in LRT samples. Temporal patterns in collagen density also indicated LRT led to a more rapid progression through the necrotic phase of healing (when the infarct is vulnerable to rupture) and earlier progression to the fibrotic phase of healing (when the infarct stabilizes). Notably, we also observed a broader region of provisional non-collagenous matrix in LRT samples during the necrotic phase of healing. Together these findings suggest LRT accelerates healing and potentially changes the spatial pattern of provisional matrix deposition during the period the heart is most susceptible to rupture events.

再灌注治疗，即恢复心肌梗死后的血流，是最有效的治疗策略之一。与早期再灌注不同，晚期再灌注治疗（LRT）与梗死面积或胶原蛋白密度的差异无关。为了评估LRT的时空效应，我们对永久性冠状动脉闭塞或闭塞3小时后的大鼠心肌组织切片进行了多模态成像。半自动分划从愈合后5天的无标记液晶偏光显微镜（PolScope）图像中识别梗死核心、边界和外围区域。采用苏木精-伊红染色切片的亮场和标准偏光显微镜图像分别测定细胞和胶原纤维密度。即使我们考虑了易损梗死边界的多种定义，其大小在LRT样本中下降得更快。胶原密度的时间模式也表明，LRT导致更快的进展，通过坏死愈合阶段（当梗死易破裂时）和更早的进展到纤维化愈合阶段（当梗死稳定时）。值得注意的是，我们还观察到，在愈合的坏死阶段，LRT样本中有更广泛的临时非胶原基质。总之，这些发现表明，在心脏最容易发生破裂事件的时期，LRT加速了愈合，并可能改变临时基质沉积的空间格局。

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引用次数: 0

COVER 4: Table of Contents/Barcode PMS 200 封面4：目录/条形码PMS 200

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-21 DOI: 10.1016/S1054-8807(25)00080-8

引用次数: 0

COVER 3: Editorial Board 封面3：编辑委员会

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-21 DOI: 10.1016/S1054-8807(25)00079-1

引用次数: 0

Comparative investigation of Cx3cr1-Expressing Cardiac Macrophages in Atrioventricular Nodes of Wild-Type and Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model 野生型和儿茶酚胺能多态性室性心动过速小鼠房室结表达cx3cr1的心脏巨噬细胞的比较研究

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-19 DOI: 10.1016/j.carpath.2025.107799

Arzuhan Koc Buyuker , Sumeyye Ozyaman , Behnaz Karadogan , Aylin Nebol , Ilknur Keskin , Esra Cagavi

Cardiac macrophages were recently discovered to regulate cardiomyocyte function at the atrioventricular (AV) nodes of healthy murine and human hearts. Macrophages and immune mediators have been implicated in ischemia-induced cardiac damage and arrhythmia; however, the relevance of macrophages in congenital arrhythmia pathogenesis remains unclear. Here, the wild-type (WT) mice and Calsequestrin2 gene null mutant (Casq2^-/-) transgenic model of catecholaminergic polymorphic ventricular tachycardia (CPVT) were comparatively evaluated for cardiac macrophage population at the histological level. The localization and density of the chemokine receptor, Cx3cr1-expressing cardiac macrophages were investigated ex vivo in heart sections from WT and Casq2^-/- mice at the AV node region using immunofluorescence, Masson’s Trichrome, and Hematoxylin-Eosin staining. Cx3cr1⁺ cardiac macrophages were localized in all cardiac layers and chambers of the heart, as well as septum and valve roots. Cx3cr1⁺ macrophages were coimmunostained and confirmed for expression of CD68 as a pan-macrophage marker. Macrophages were detected in close proximity to the cTnT⁺ cardiomyocytes in the myocardium of both WT and Casq2^-/- transgenic mice. Macrophage clusters were abundantly observed in the Hcn4 immunoreactive AV node region in healthy murine hearts. Subsequent quantification of signal intensities of Cx3cr1⁺ cardiac macrophages in the AV nodes in the Casq2^-/- transgenic mice was significantly lower than in WT mice. These results demonstrated a decline in Cx3cr1⁺ cardiac macrophages in AV node regions of CPVT mouse hearts, which could imply a potential contribution to arrhythmia. Our findings could serve as a valuable source for future functional investigations of macrophages in the pathogenesis of congenital arrhythmia.

最近发现心脏巨噬细胞可调节健康小鼠和人类心脏房室（AV）节点的心肌细胞功能。巨噬细胞和免疫介质与缺血引起的心脏损伤和心律失常有关；然而，巨噬细胞在先天性心律失常发病机制中的相关性尚不清楚。本研究在组织学水平上比较了野生型（WT）小鼠和Calsequestrin2基因零突变体（Casq2-/-）转基因儿茶酚胺能多态性室性心动过速（CPVT）模型的心肌巨噬细胞群。采用免疫荧光、马松三色染色和苏木精-伊红染色，研究WT和Casq2-/-小鼠心脏切片中表达趋化因子受体cx3cr1的心脏巨噬细胞在房室结区域的定位和密度。Cx3cr1+心脏巨噬细胞分布于心脏各层和腔室，以及隔膜和瓣根。Cx3cr1+巨噬细胞共免疫染色，证实CD68作为泛巨噬细胞标志物表达。在WT和Casq2-/-转基因小鼠的心肌中，在cTnT+心肌细胞附近检测到巨噬细胞。在健康小鼠心脏Hcn4免疫反应性房室结区大量观察到巨噬细胞簇。随后定量检测Casq2-/-转基因小鼠心室房室淋巴结中Cx3cr1+心脏巨噬细胞的信号强度显著低于WT小鼠。这些结果表明CPVT小鼠心脏房室结区域Cx3cr1+心脏巨噬细胞的下降，这可能意味着心律失常的潜在贡献。我们的发现可以为未来巨噬细胞在先天性心律失常发病机制中的功能研究提供有价值的来源。

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引用次数: 0

Characterization of the clinical, histopathologic, and immunohistochemical features of large papillary fibroelastomas and their S100-expressing spindle cell component and its potential relationship to cardiac valvular interstitial cells 大乳头状纤维弹性瘤的临床、组织病理学和免疫组织化学特征及其表达s100的梭形细胞成分及其与心脏瓣膜间质细胞的潜在关系

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-19 DOI: 10.1016/j.carpath.2025.107800

Faye Victoria C. Casimero , James R. Stone

Papillary fibroelastomas (PFEs) are uncommon, benign cardiac tumors most commonly measuring less than 1 cm and arising on cardiac valves. Large PFEs (≥1 cm), though clinically significant due to embolic potential, remain less well characterized. This study aimed to define the clinical, histopathologic, and immunohistochemical features of large PFEs, with a focus on the spindle cell component. A retrospective analysis was performed on 24 large PFEs resected between 2011 and 2024. Histologic analysis included hematoxylin and eosin staining, elastic staining, and immunohistochemistry for S100, calretinin, and CD31. The presence of a spindle cell component was defined as the presence of ≥10 non-surface spindle cells in a single 400x high-power field (HPF). S100⁺ spindle cells were quantified across 10 HPFs. Myxomatous mitral valves were also evaluated for comparison. Large PFEs were located in both cardiac chambers (n = 13) and on valves (n = 11). The median patient age was 69 years, and in all cases the tumor had been identified on imaging. Embolic events occurred in three (13%) of the cases, all from left-sided lesions. Seventeen (71%) of the large PFEs contained a spindle cell component, with significantly higher S100⁺ spindle cell density in valvular PFEs compared to chamber PFEs (median 14 vs. 1 per HPF; P = 0.045). In the large PFEs, CD31 was diffusely positive in surface endothelium, with variable endothelial S100 co-expression. There was only rare calretinin staining. The valvular interstitial cells in valves with myxomatous degeneration were also diffusely positive for S100. The presence of S100⁺ spindle cells in large PFEs suggests that a process similar to valvular interstitial cell activation and/or endothelial-to-mesenchymal transition may be important in PFE tumor pathogenesis.

乳头状纤维弹性瘤（pfe）是一种罕见的良性心脏肿瘤，最常见的是直径小于1厘米，起源于心脏瓣膜。较大的pfe(≥1cm)，虽然由于栓塞的可能性而具有临床意义，但其特征仍然较少。本研究旨在确定大型pfe的临床、组织病理学和免疫组织化学特征，重点关注梭形细胞成分。回顾性分析了2011年至2024年间切除的24例大pfe。组织学分析包括苏木精和伊红染色，弹性染色，免疫组化S100， calretinin和CD31。纺锤体细胞成分的存在被定义为在单个400倍高倍场（HPF）中存在≥10个非表面纺锤体细胞。在10个hpf中对S100+纺锤体细胞进行定量。粘液瘤二尖瓣也进行了比较评估。大pfe位于两个心室（n = 13）和瓣膜（n = 11）。患者的中位年龄为69岁，所有病例的肿瘤都在影像学上被发现。栓塞事件发生在3例（13%）病例中，均来自左侧病变。17个（71%）大型pfe含有纺锤细胞成分，与腔室pfe相比，瓣膜pfe的S100+纺锤细胞密度显著更高（中位数为14比1 / HPF； P = 0.045）。在大的pfe中，CD31在表面内皮呈弥漫性阳性，内皮细胞S100共表达变化。仅有罕见的calcaltin染色。黏液瘤变性的瓣膜间质细胞S100也呈弥漫性阳性。大PFE中S100+梭形细胞的存在表明，类似于瓣膜间质细胞活化和/或内皮向间质转化的过程可能在PFE肿瘤发病过程中起重要作用。

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引用次数: 0

Transforming growth factor-beta (TGF-β) in the pathogenesis of hereditary thoracic aneurysm disorders 转化生长因子-β (TGF-β)在遗传性胸动脉瘤发病机制中的作用

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-13 DOI: 10.1016/j.carpath.2025.107790

Wendy A. Espinoza Camejo , Emily E. Bramel , Elena Gallo MacFarlane

The transforming growth factor-beta (TGF-β) signaling pathway regulates biological processes critical to embryonic development and tissue homeostasis, including cell proliferation, differentiation, adhesion and migration. Perturbations in TGF-β signaling are linked to a wide range of human diseases, including those affecting the cardiovascular system. This review summarizes decades-long evidence documenting the importance of this pathway to hereditary forms of aortic disease and presents current perspectives on its role in pathogenesis. We discuss the dual role of TGF-β signaling in aneurysm progression, and its protective and maladaptive effects on vascular smooth muscle cells (VSMCs) phenotype, extracellular matrix (ECM) composition, and other disease-relevant signaling pathways.

转化生长因子-β (TGF-β)信号通路调节对胚胎发育和组织稳态至关重要的生物过程，包括细胞增殖、分化、粘附和迁移。TGF-β信号的扰动与多种人类疾病有关，包括那些影响心血管系统的疾病。这篇综述总结了几十年来证明这一途径在主动脉疾病遗传形式中的重要性的证据，并提出了其在发病机制中的作用的最新观点。我们讨论了TGF-β信号在动脉瘤进展中的双重作用，以及其对血管平滑肌细胞（VSMCs）表型、细胞外基质（ECM）组成和其他疾病相关信号通路的保护和适应性不良作用。

引用次数: 0

The SCVP and AECVP 'Seaport criteria' for lymphocytic myocarditis: Retrospective application to an autopsy cohort. 淋巴细胞性心肌炎的SCVP和AECVP“海港标准”：回顾性应用于尸检队列。

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.carpath.2025.107763

Sarah Parsons, Hans H de Boer

Background: 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.

Objective: To assess the practical applicability of the Seaport criteria in a retrospective cohort of forensic autopsy cases with myocardial lymphocytic-predominant inflammation.

Methods: 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.

Results: 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.

Conclusions: 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.

背景：在非活检标本中诊断淋巴细胞性心肌炎仍然具有挑战性，因为样本可变性、组织学的主观解释和缺乏标准化标准。2025年，心血管病理学会（SCVP）和欧洲心血管病理协会（AECVP）提出了“海港标准”来解决这些限制。目的：评价Seaport标准在心肌淋巴细胞显性炎症的法医尸检病例回顾性队列中的实际适用性。方法：根据Seaport标准，对93例以淋巴细胞为主的心肌炎症进行重新评价。这些病例中的死亡归因于心肌炎（n=45）、原因不明（n=34）或药物毒性（n=14）。我们评估了对推荐技术要求的依从性，将炎症重新分类为弥漫性、多灶性、局灶性心肌炎或不明意义淋巴细胞浸润（LIUS），并回顾了原始组织学描述。结果：多数病例（82%）符合最低技术抽样标准。儿科病例不成比例地不符合采样要求，但不是由于心肌采样不足。原始组织学报告在术语和细节上有很大差异，心肌细胞损伤的报告不一致，并且缺乏根据海港标准进行分级的足够信息。弥漫性心肌炎36例，多灶性心肌炎27例，局灶性心肌炎2例，LIUS 28例。在以心肌炎作为死亡原因的病例中，最常见的诊断是弥漫性心肌炎（33/45），而LIUS在药物相关和未确定的队列中最常见。肌细胞损伤有时难以解释。结论：Seaport标准对尸检心脏淋巴细胞性心肌炎分类是可行的，有可能规范组织学评估，从而提高诊断的一致性。然而，在识别肌细胞损伤方面仍然存在挑战。建议进一步进行前瞻性多中心验证。

{"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}

引用次数: 0

Aortic wall lamellar structure in phylogeny and in humans: insights from bicuspid and tricuspid aortic valve morphology 系统发育和人类的主动脉壁板层结构：来自二尖瓣和三尖瓣主动脉瓣形态的见解。

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-10-31 DOI: 10.1016/j.carpath.2025.107789

Nora Bacour , Mohammad Zafar , Nicole Kargin , Bulat Zinganshin , Robert Poelmann , Robert J.M. Klautz , John Elefteriades , Nimrat Grewal

Objective

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.

Methods

Non-dilated ascending aortic wall samples (n = 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.

Results

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.

Conclusion

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.

目的：尽管有大量关于主动脉病变的文献，但相对较少关注主动脉壁的板层结构，包括这些层的数量和分布。本研究比较了患有二尖瓣（BAV）和三尖瓣主动脉瓣（TAV）的个体的主动脉板层组织，并对哺乳动物和成人主动脉板层的文献进行了综述。方法：对83例未扩张的升主动脉壁样本进行分析，这些样本来自胚胎至72岁的个体，分为6个年龄组。此外，还对不同物种间的片层数进行了文献综述。结果：早产儿主动脉弹性片结构完整，无明显病理特征。相反，成人主动脉表现为进行性弹性纤维病变。随着年龄增长，叶片数量增加；新生儿的计数最低，在幼儿中达到峰值，在青少年中逐渐减少。此外，与TAV患者相比，BAV患者表现出更薄的内膜层和更少的弹性片层。我们的文献综述表明，哺乳动物的瓣片数量与体型和主动脉半径相关，体型越小的动物瓣片越少。人类的胸升主动脉有45到78个弹性薄片，而降主动脉和腹主动脉的层数更少。结论：主动脉壁弹性薄片的数量受年龄和瓣膜形态的影响。BAV患者片层少于TAV患者，这可能导致临床结果的差异。在老年人中，年龄相关性板层变性可能增加主动脉病变的风险。

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引用次数: 0

Quantified calcification in rat aortic valves isolated with the sinus of Valsalva coordinates with calciprotein particles formation 与Valsalva窦分离的大鼠主动脉瓣定量钙化与钙蛋白颗粒形成相协调。

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-10-21 DOI: 10.1016/j.carpath.2025.107788

Shota Morikane , Koichi Ishida , Naoki Ashizawa , Tetsuya Taniguchi , Masaya Matsubayashi , Naoki Kurita , Seiichi Kobashi , Takashi Iwanaga

Background

Aortic valve sclerosis, in which calcification is a major pathogenesis, is a serious complication of chronic kidney disease. In small animal experiments, it is difficult to evaluate aortic valve calcification quantitatively except for diagnostic imaging because of their small size. In this study, to quantify rat aortic valve calcification, we isolated rat whole aortic valves and verified whether its calcification has own characteristics by investigating a relationship with calciprotein particles (CPP) formation, which is suggested as a biomarker of tissue calcification.

Methods

Human aortic valve interstitial cells (HAVICs) were cultured in a high-phosphate medium with or without two bisphosphonates, and their calcification was determined. The rats were injected with vitamin D to induce calcification and were treated with the bisphosphonates. The whole aortic valve was collected by trimming from the base of the aortic arch to the heart (including the sinus of Valsalva), and calcification and CPP formation in the serum were measured.

Results

Calcification of HAVICs was inhibited by two bisphosphonates accompanied by inhibition of CPP formation. In vitamin D-treated rats, calcium content of the region collected as aortic valve was equivalent to that of the aorta and higher than that of the heart, whereas calcification suppression by the bisphosphonates in the collected region was equivalent to that in the heart and stronger than that in the aorta. The bisphosphonate-induced inhibition percentages of calcification in the collected region correlated with that of CPP formation, and the correlation was different from that observed in the aorta and heart.

Conclusions

The collecting whole aortic valve allowed easy and accurate assessment of calcification, which was quantitatively supported by the close correlation with CPP formation, and showed different characteristic from those in the aorta and heart. The results will provide crucial information for exploring the mechanism of valve calcification and for the discovery of calcification inhibitors.

背景：主动脉瓣硬化是慢性肾脏疾病的严重并发症，其中钙化是主要发病机制。在小动物实验中，由于主动脉瓣体积小，除了诊断性影像学外，很难定量评价其钙化程度。本研究为了量化大鼠主动脉瓣钙化，我们分离了大鼠整个主动脉瓣，通过研究其钙化与钙蛋白颗粒（calprotein particles， CPP）形成的关系来验证其钙化是否具有自身的特征，钙蛋白颗粒被认为是组织钙化的生物标志物。方法：将人主动脉瓣间质细胞（HAVICs）在含或不含两种双磷酸盐的高磷酸盐培养基中培养，观察其钙化情况。给大鼠注射维生素D诱导钙化，并用双膦酸盐处理。从主动脉弓基部至心脏（包括Valsalva窦），采用切边法采集整个主动脉瓣，测定血清钙化及CPP形成情况。结果：两种双膦酸盐可抑制HAVICs的钙化，同时抑制CPP的形成。在维生素d处理的大鼠中，主动脉瓣收集区域的钙含量与主动脉相当，高于心脏，而双膦酸盐在收集区域的钙化抑制作用与心脏相当，强于主动脉。双膦酸盐对采集区钙化的抑制率与CPP形成的抑制率相关，但与主动脉和心脏的相关性不同。结论：全主动脉瓣采集可以方便、准确地评估钙化，与CPP形成密切相关，定量支持钙化，且与主动脉和心脏的钙化表现出不同的特点。该结果将为探索瓣膜钙化机理和发现钙化抑制剂提供重要信息。

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引用次数: 0

Pathological capillary analysis of ischemia with non-obstructive coronary arteries in a Fabry disease patient receiving enzyme replacement therapy 接受酶替代治疗的法布里病非阻塞性冠状动脉缺血的病理毛细血管分析。

IF 1.9 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Pathology

Pub Date : 2025-10-09 DOI: 10.1016/j.carpath.2025.107786

Hiromitsu Kanamori, Genki Naruse, Shingo Minatoguchi, Maya Ishiguro, Akihiro Yoshida, Hiroyuki Okura

Fabry disease is a lysosomal disorder caused by an α-galactosidase A deficiency, which often causes angina in the absence of epicardial coronary artery stenosis. It is conceivable that epicardial and microvascular coronary dysfunction due to globotriaosylceramide and related glycoshingolipid accumulation within the vasculature causes ischemia with non-obstructive coronary arteries (INOCA). However, the precise histology remained unknown. We present the case of a 44-year-old male diagnosed with Fabry disease and treated with enzyme replacement therapy (ERT), who was referred to our cardiology department after complaining of exertional and rest precordial discomfort. Electrocardiography showed left ventricular hypertrophy (LVH) with strained ST segment depression. Echocardiography showed normal wall motion with diffuse LVH. Although coronary angiography showed no organic stenosis, spasms were provoked by intracoronary ergonovine injection. Invasive assessment of the microvasculature physiology showed the mean index of microcirculatory resistance to be 42 and the mean coronary flow reserve to be 1.6, which is indicative of coronary microvascular dysfunction. Endomyocardial biopsy revealed abundant accumulation of lamellar bodies within both cardiomyocytes and capillary pericytes, but not endothelial cells, suggesting microvascular flow disruption attributable to pericyte contraction and capillary constriction. This case highlights INOCA associated with a microvascular lesion related to Fabry disease in a patient receiving ERT as well as the need to develop therapies targeting the capillary circulation.

法布里病是一种由半乳糖苷酶a缺乏引起的溶酶体疾病，在没有心外膜冠状动脉狭窄的情况下常引起心绞痛。可以想象，心外膜和微血管冠状动脉功能障碍是由于血管内的球三神经酰胺和相关的糖鞘脂积累引起的非阻塞性冠状动脉缺血（INOCA）。然而，精确的组织学仍然未知。我们提出一个44岁的男性诊断为法布里病和治疗的酶替代疗法（ERT），谁被转介到我们的心脏科后，抱怨劳累和休息心前不适。心电图显示左室肥厚伴ST段压迫。超声心动图显示壁运动正常，伴有弥漫性LVH。尽管冠状动脉造影未显示器质性狭窄，但冠状动脉内注射麦角碱引起痉挛。微血管生理有创评估显示，微循环阻力平均指数为42，平均冠状动脉血流储备为1.6，提示冠状动脉微血管功能障碍。心肌内膜活检显示心肌细胞和毛细血管周细胞内均有丰富的板层体积聚，但内皮细胞内没有，提示微血管流动中断可归因于周细胞收缩和毛细血管收缩。本病例强调了接受ERT的患者中与法布里病相关的微血管病变相关的INOCA，以及开发针对毛细血管循环的治疗的必要性。

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引用次数: 0