Acute lung injury (ALI) is characterized by impaired alveolar epithelial barrier function and mitochondrial dysfunction in type II alveolar epithelial cells (AT2 cells). Ceramide synthase 6 (CerS6), a key enzyme in sphingolipid metabolism responsible for generating C16:0 ceramide, has not previously been implicated in ALI. This study reveals that CerS6 expression is significantly upregulated in AT2 cells during lipopolysaccharide (LPS)- and cecal ligation and puncture (CLP)-induced ALI. Specific knockout of CerS6 in AT2 cells attenuates apoptosis, inflammation, oxidative stress, and barrier disruption in an ALI mouse model while preserving mitochondrial function. Mechanistically, CerS6 directly interacts with the mitophagy receptor BNIP3, disrupting its binding to LC3 and thereby inhibiting mitophagy. The impaired mitochondrial clearance mechanism promotes cytoplasmic release of mtDNA and activates the STING/NLRP3 signaling cascade. RNA-Seq further confirmed that CerS6 knockdown suppressed the STING/NLRP3 pathway and upregulated BNIP3. Notably, CerS6 metabolite C16:0 ceramide also participated in these effects, reinforcing the pivotal role of sphingolipid metabolism in linking mitochondrial stress to innate immune activation. In summary, this study establishes CerS6 as a core driver of mitochondrial dysfunction and redox imbalance in acute lung injury, and indicates that both CerS6 and C16:0 ceramide may serve as potential therapeutic targets.

BACKGROUND:Diabetic wound healing impairment poses a serious threat to patient health, underscoring the urgent need for effective therapies. Aloe polysaccharides (APs), one of the main bioactive components of Aloe vera, have been reported to exhibit diverse biological activities, including antibacterial, antioxidant, anti-obesity, and anti-tumor effects. However, their role in diabetic wound repair remains unclear, limiting its translational potential. PURPOSE:This study aims to clarify the therapeutic effect and specific mechanism of APs on diabetic wound healing. STUDY DESIGN AND METHODS:Cellular transcriptome sequencing was used to analyze APs' effect on pathway activation in high glucose (HG)-exposed macrophages. In vitro experiments detected APs' effect on HG-pretreated macrophage-conditioned medium-induced fibroblast migration impairment and their role in promoting macrophage M2 polarization (NLRP3 agonist for pathway verification). A diabetic mouse wound model was established for in vivo validation of APs' effect on wound healing. Animal tissue transcriptome sequencing was conducted to compare with in vitro results and confirm APs' anti-inflammatory mechanism. RESULTS:Cellular transcriptome sequencing showed APs significantly suppress NLRP3 inflammasome pathway activation in HG-exposed macrophages. In vitro, APs ameliorate fibroblast migration impairment and promote macrophage M2 polarization (effect reversed by NLRP3 agonist). In diabetic mice, APs accelerate wound closure, attenuate local inflammation and enhance angiogenesis. Animal tissue transcriptome sequencing results matched in vitro findings, confirming APs inhibit NLRP3 pathway as their anti-inflammatory mechanism in vitro and in vivo. CONCLUSION:Our study elucidates that APs facilitate diabetic wound healing by modulating macrophage M2 polarization through inhibition of NLRP3 inflammasome activation.

Immunosuppression is a distinctive condition resulting from sepsis, marked by impaired immune response and immune dysregulation, with a poor prognosis. PRC1, a mitotic regulatory protein, is associated with immune suppression within the tumor microenvironment. However, the role of PRC1 in septic immunosuppression remains unclear. This research aimed to explore the implication and potential mechanism of PRC1 in septic immunosuppression. Dataset GSE95233 and GSE65682 were used to validate the expression and prognostic value of PRC1 in sepsis patients. LPS was used to stimulate naïve or endotoxin-tolerant THP-1 and BMDMs. PRC1 expression was measured in by RT-qPCR and Western blot. Small interfering RNA was used for PRC1 knockdown in THP-1. The phosphorylated STAT3 and active β-catenin was detected by Western blot. The expression levels of cytokines and surface markers of macrophages were validated by RT-qPCR. β-catenin inhibitor MSAB and agonist SKL2001 were used to explore the functional relationship among relevant molecules. PRC1 expression was increased in sepsis non-survivors in both dataset GSE95233 and GSE65682, and increased PRC1 expression was associated with increased 28-days septic mortality. PRC1 expression was elevated in endotoxin-tolerant macrophages rather than naïve macrophages. Sustained phosphorylation of STAT3 was detected in endotoxin-tolerant macrophages. Increased PRC1 expression maintained the phosphorylated STAT3 level via a β-catenin-dependent mechanism, which was reversed by β-catenin inhibitor MSAB. PRC1 knockdown could reduce STAT3 phosphorylation and restore inflammatory responses in endotoxin-tolerant macrophages, while this effect was eliminated by β-catenin agonist SKL2001. Septic microenvironment promoted the expression of PRC1 in endotoxin-tolerant macrophages. Our data demonstrated that PRC1 is upregulated in endotoxin-tolerant macrophages, and that increased PRC1 expression maintains STAT3 activation via a β-catenin-dependent mechanism and impairs inflammatory response of macrophages during septic immunosuppression. Targeting PRC1/β-catenin/ STAT3 could represent a novel strategy for the management of septic immunosuppression and restore the inflammatory response of endotoxin-tolerant macrophages.

Diabetic patients are considered as the high risk population to develop critical limb ischemia (CLI), a peripheral vascular disease (PVD) resulted from atherosclerosis. Cuproptosis is a novel copper-dependent cell death that has shown the regulatory role in diabetes, while its effect on diabetic CLI has not been explored yet. In this study, Diabetic CLI mice was induced by femoral artery ligation (FAL) on diabetic mice. Endothelial injury in diabetic CLI was mimicked in human microvascular endothelial cells (HMEC-1) via the induction with high glucose (HG) and nutrient deprivation (ND). Besides, copper chelator Ammonium Tetrathiomolybdate (TM), which has shown the anti-cuproptosis property, was administrated to explore its potential effects on diabetic CLI mice and HG/ND-induced HMEC-1 cells. Strikingly, obvious cuproptosis was found in the gastrocnemius muscles of diabetic CLI mice and HG/ND-induced HMEC-1 cells, as evidenced by the copper overload and dysregulated cuproptosis-related proteins (such as Fe-S cluster proteins, copper exporter ATP7A, and copper importer SLC31A1). More importantly, TM protected against the hindlimb ischemic damages in diabetic CLI mice and alleviated cuproptosis-associated cell deaths in HG/ND-induced HMEC-1 cells. In summary, this study indicates the involvements of cuproptosis in diabetic CLI, and provides novel insights into copper chelator TM on diabetic CLI therapy.

BACKGROUND:Aortic dissection (AD) is a life-threatening cardiovascular condition characterized by high morbidity and mortality rates. However, the molecular mechanism of intracellular pH in AD development has not been fully elucidated. In this study, the role of carbonic anhydrase 9 (CA9) in VSMCs intracellular pH and the regulatory mechanism were investigated. METHODS:Cell viability was examined by cell counting kit-8 (CCK-8) and intracellular pH was detected by BCECF-AM probe. The regulation of CA9 transcription by HIF-1α was measured by Cut &run-qPCR assay. The levels of CA9, HIF-1α, MMP2 and α-SMA were evaluated by RT-qPCR, Western blot and Immunofluorescence. RESULTS:Our results demonstrated that CA9 was significantly upregulated in AD tissues, primarily localized in VSMCs, and associated with increased MMP2 levels, while α-SMA levels decreased. Silencing CA9 in VSMCs resulted in reduced cell viability and increased intracellular pH. Additionally, we found that HIF-1α was upregulated in AD, regulating CA9 expression in VSMCs. Treatment with JTC801 in a BAPN-induced mouse model reduced CA9 and HIF-1α expression, improving survival and decreasing AD incidence. CONCLUSION:This study establishes CA9 as a hypoxia-responsive mediator of pH dysregulation in AD, modulated by HIF-1α. Targeting the HIF-1α/CA9 axis with JTC801 presents a novel therapeutic strategy to restore VSMC homeostasis and ECM integrity. These findings advance our understanding of intracellular pH in AD and highlight this approach may be a potential therapeutic target.

The installation of arterial stents refers to the use of stents (also known as vascular stents) to maintain the patency of arteries during the treatment of arterial stenosis or blockage. Arterial stents are typically made of metal or polymer materials and are structured as a mesh that provides support within the blood vessel, preventing it from collapsing again after interventional treatment. The installation of arterial stents is an effective interventional therapy that can significantly improve symptoms caused by arterial stenosis or blockage and enhance the quality of life for patients. Endovascular therapy has become increasingly important for treating both thoracic and abdominal aortic diseases. A critical aspect of this procedure is the precise positioning of stents and complete isolation of the pathology. To enhance stent placement accuracy, we propose a deep learning model called the Double Branch Medical Image Detector (DBMedDet), which offers real-time guidance for stent placement during implantation surgeries. The DBMedDet model features a parallel dual-branch edge feature extraction network, a bidirectional feedback feature fusion neck sub-network, as well as a position detection head and a classification head specifically designed for thoracic and abdominal aortic stents. The model has achieved a detection Mean Average Precision (mAP) of 0.841 (mAP@0.5) and a real-time detection speed of 127 Frames Per Second (FPS). For mAP@0.5, when employing 5-fold cross-validation, DBMedDet demonstrates superior performance compared to several YOLO models, achieving improvements of 4.88% over YOLOv8l, 4.61% over YOLOv8m, 3.20% over YOLOv8s, 6.23% over YOLOv8n, 6.09% over YOLOv10s, 3.92% over YOLOv9s, 3.20% over YOLOv8s, 3.00% over YOLOv7tiny, and 5.01% over YOLOv5s. This study presents a precise and easily implementable method for the automatic detection of stent placement limits in the thoracic and abdominal aorta. The model can be applied in various areas such as coronary intervention therapy, peripheral vascular intervention therapy, cerebrovascular intervention therapy, postoperative monitoring and follow-up, and medical training and education. By utilizing real-time imaging guidance and deep learning models (such as DBMedDet), stent placement procedures in these application areas can be performed with greater precision and safety, thereby enhancing patient treatment outcomes and quality of life.

Objective: Cardiac hypertrophy, a key feature and predisposing factor of heart failure, is mainly controlled by complex signaling cascades. Growth differentiation factor 6 (GDF6) plays critical roles in cell growth and cardiovascular homeostasis; however, its role and underlying mechanisms in cardiac hypertrophy remain unclear. Methods: Mice were intravenously injected with adeno-associated virus serotype 9 to overexpress and knock down GDF6 in murine hearts and then exposed to transverse aortic constriction (TAC) surgery to generate pressure overload-induced cardiac hypertrophy. Echocardiographic, histological, and molecular analyses were performed to decipher the alterations to cardiac hypertrophy. In addition, neonatal rat ventricular myocytes (NRVMs) were isolated and stimulated with phenylephrine (PE) to further validate its involvement in hypertrophic growth of cardiomyocytes. Results: GDF6 expression was elevated in murine hearts and NRVMs by ROS production under hypertrophic stimuli. GDF6 knockdown aggravated, while GDF6 overexpression attenuated, pressure overload-induced cardiac hypertrophy, inflammation, and dysfunction in vivo. Meanwhile, we found that GDF6 also prevented PE-induced hypertrophic growth of NRVMs in vitro. Mechanistically, GDF6 activated AMPKα to exert cardioprotective effects, and AMPKα inhibition significantly blocked the anti-hypertrophic effects of GDF6. Further studies showed that GDF6 activated AMPKα through the cAMP/Epac1 pathway, and that Epac1 knockdown abolished the protective effects of GDF6 against TAC- or PE-induced cardiac hypertrophy in vivo and in vitro. Conclusions: In general, our findings, for the first time, define GDF6 as a negative regulator of cardiac hypertrophy and show that supplementation of GDF6 may be of great therapeutic interest for heart failure.

Aortic dissection is characterized pathologically by aortic medial degeneration (AMD) where disturbance of mitochondrial dynamics may be involved. Stearic acid (SA) can promote mitochondrial fusion and improve mitochondrial function. Here we established an AMD mouse model through oral administration of β-aminopropionitrile (BAPN) and a cellular model by treating primary vascular smooth muscle cells (VSMCs) with Angiotensin-II to explore the potential role of SA in AMD. Our results showed SA reduced AMD and prolonged survival of BAPN-treated mice. Excessive mitochondrial fission was observed during AMD both in vivo and in vitro, and SA reduced mitochondrial fission and increased fusion. Additionally, SA promoted expression of contractile phenotype markers of VSMCs. At the molecular level, SA reduced AMD by inhibiting JNK/MAPK signaling. Our study suggests SA can promote mitochondrial fusion and increase the contractile phenotype of VSMCs by inhibiting JNK/MAPK signaling, thereby reducing AMD formation and possibly the consequent risk of aortic dissection.

It is well known that aortic dissection (AD) is a very aggressive class of vascular diseases. S-adenosylmethionine (SAM) is an autophagy inhibitor with anti-inflammatory and anti-oxidative stress effects; however, the role of SAM in AD is unknown. In this study, we constructed an animal model of AD using subcutaneous minipump continuous infusion of AngII-induced ApoE-/-mice and a cytopathic model using AngII-induced primary vascular smooth muscle cells (VSMCs) to investigate the possible role of SAM in AD. The results showed that mice in the AngII + SAM group had significantly lower AD incidence, significantly prolonged survival, and reduced vascular elastic fiber disruption compared with mice in the AngII group. In addition, SAM significantly inhibited autophagy in vivo and in vitro. Meanwhile, SAM also inhibited the cellular phenotypic switch, mainly by up regulating the expression levels of contractile marker proteins [α-smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α)] and down regulating the expression levels of synthetic marker proteins [osteoblast protein (OPN), matrix metalloproteinase-2 (MMP2), and matrix metalloproteinase-9 (MMP9)]. Molecularly, SAM inhibited AD formation mainly by activating the PI3K/AKT/mTOR signaling pathway. Using a PI3K inhibitor (LY294002) significantly reversed the protective effect of SAM in AngII-induced mice and VSMCs.Our study demonstrates the protective effect of SAM on mice under AngII-induced AD for the first time. SAM prevented AD formation mainly by inhibiting cellular phenotypic switch and autophagy, and activation of the PI3K/AKT/mTOR signaling pathway is a possible molecular mechanism. Thus, SAM may be a novel strategy for the treatment of AD.

Acute cardiac rejection remains a significant challenge in the post-transplant period, necessitating meticulous monitoring and timely intervention to prevent graft failure. Thus, the goal of the present study was to identify novel biomarkers involved in acute cardiac rejection, paving the way for personalized diagnostic, preventive, and treatment strategies. A total of 809 differentially expressed genes were identified in the GSE150059 dataset. We intersected genes selected by analysis of variance, recursive feature elimination, least absolute shrinkage and selection operator, and random forest classifier to identify the most relevant genes involved in acute cardiac rejection. Thus, HCP5, KLRD1, GZMB, PLA1A, GNLY, and KLRB1 were used to train eight machine learning models: random forest, logistic regression, decision trees, support vector machines, gradient boosting machines, K-nearest neighbors, XGBoost, and neural networks. Models were trained, tested, and validated on the GSE150059 dataset (MMDx-based diagnosis of rejection). Eight algorithms achieved great performance in predicting acute cardiac rejection. However, all machine learning models demonstrated poor performance in two external validation sets that had rejection diagnosis based on histology: merged GSE2596 and GSE4470 dataset and GSE9377 dataset, thus highlighting differences between these two methods. According to SHAP and LIME, KLRD1 and HCP5 were the most impactful genes.

Abdominal aortic aneurysm (AAA) is a dangerous condition affecting the aorta. Macrophage pyroptosis, phenotypic transformation, and apoptosis of aortic smooth muscle cells (ASMCs) are pivotal mechanisms in AAA pathogenesis. This study explores how Gasdermin B (GSDMB) regulates macrophage non-canonical pyroptosis and its impact on the phenotypic transformation and apoptosis of ASMCs, thereby unveiling the role of GSDMB in AAA pathogenesis. Immunofluorescence analysis was used to assess the expression levels and localization of GSDMB, cysteinyl aspartate-specific protease-4 (Caspase-4), and N-terminal of cleaved GSDMD (N-GSDMD) in AAA tissues. A cell model that mimics macrophage non-canonical pyroptosis was established by treating THP-1 cells with lipopolysaccharide (LPS). THP-1 cells with reduced or increased GSDMB were generated using small interfering RNA (siRNA) or plasmids. Co-culture experiments involving THP-1 cells and HASMCs were conducted to explore the impact of GSDMB on HASMCs. The mitochondrial reactive oxygen species (mtROS) scavenger Mito-TEMPO lowered mtROS levels in THP-1 cells. Our findings revealed that GSDMB was significantly upregulated in AAA macrophages, which was accompanied by robust non-canonical pyroptosis. THP-1 cells showed non-canonical pyroptosis in response to LPS, which was accompanied by an increase in GSDMB. Further research demonstrated that altering GSDMB, either by knockdown or overexpression, can affect macrophage non-canonical pyroptosis as well as the phenotypic transformation and apoptosis of HASMCs. LPS-induced non-canonical pyroptosis in THP-1 cells was associated with an increase in mtROS, whereas Mito-TEMPO effectively decreased non-canonical pyroptosis and the expression of GSDMB. These findings suggest that GSDMB plays a role in AAA macrophage non-canonical pyroptosis, which influences the phenotypic transformation and apoptosis of HASMCs. The mtROS-Dynamin-Related Protein 1 (Drp1) axis is likely to regulate the GSDMB-mediated non-canonical pyroptosis.

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.

BACKGROUND:Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS:The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS:The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.

Background:Glucose transporter 10 (GLUT10) is encoded by the SLC2A10 gene. Our recent investigations have shown that GLUT10 is not only involved in glucose metabolism but also involved in the body's immune response to cancer cells. However, the role of GLUT10 in tumor prognosis and in tumor immunity has not been reported.Methods:We knocked down SLC2A10 and performed transcriptome sequencing to analyse the biological function of GLUT10 and found that GLUT10 may be involved in immune signaling. Then, we studied the expression level of SLC2A10 in cancers by the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We also evaluated the prognostic potential of SLC2A10 in different cancers using the Kaplan‒Meier plotter database and PrognoScan online software. The correlations between SLC2A10 expression and immune infiltrates were analysed by TIMER. In addition, correlations between SLC2A10 expression and gene marker sets of immune infiltrates were analysed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). Immunofluorescence staining of cyclooxygenase-2 (COX-2) and GLUT10 in lung cancer tissue and adjacent tissue was performed to confirm our findings from the database research.Results:Knocking down SLC2A10 widely activated immune and inflammatory signaling. SLC2A10 was abnormally expressed in several tumors. The expression level of SLC2A10 was closely correlated with cancer prognosis. Low SLC2A10 expression was related to poorer prognosis and increased malignancy of lung cancer. Lung cancer patients with low expression of SLC2A10 have a much shorter median survival time than patients with high expression of SLC2A10. SLC2A10 expression is closely related to the infiltration of different types of immune cells, particularly macrophages. Both database research and lung cancer sample research revealed that GLUT10 might modulate immune cell infiltration via the COX-2 pathway.Conclusions:By transcriptome experiments, database studies, and human sample studies, we found that GLUT10 is a new immune signaling molecule involved in tumor immunity, especially in the immune cell infiltration of lung adenocarcinoma (LUAD). GLUT10 may modulate the immune cell infiltration of LUAD via the COX-2 pathway.

HomeCirculation: Cardiovascular ImagingVol. 16, No. 3Rosai-Dorfman Disease Involving the Descending Aorta Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBRosai-Dorfman Disease Involving the Descending Aorta Luocheng Li, Zhiwei Wang, Lin Liu, Hongbing Wu, Zongli Ren and Jingping Yuan Luocheng LiLuocheng Li https://orcid.org/0000-0001-8884-5670 Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Zhiwei WangZhiwei Wang Correspondence to: Zhiwei Wang, MD, Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 99, Zhangzhidong Rd, Wuchang District, Wuhan, China 430060. Email E-mail Address: [email protected] https://orcid.org/0000-0001-5643-9344 Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Lin LiuLin Liu Department of Pathology (Lin Liu, J. Yuan), Renmin Hospital of Wuhan University, Wuhan, China. , Hongbing WuHongbing Wu Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. , Zongli RenZongli Ren Department of Cardiovascular Surgery (Luocheng Li, Z. Wang, H. Wu, Z. Ren), Renmin Hospital of Wuhan University, Wuhan, China. and Jingping YuanJingping Yuan Department of Pathology (Lin Liu, J. Yuan), Renmin Hospital of Wuhan University, Wuhan, China. Originally published8 Feb 2023https://doi.org/10.1161/CIRCIMAGING.122.014582Circulation: Cardiovascular Imaging. 2023;16Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: February 8, 2023: Ahead of Print A 41-year-old female patient presented to the emergency department in our hospital with a 1-year history of hypertension and dizziness and headache for the last 7 hours. According to her medical record, she was admitted to the Cardiology Department in our hospital for sudden onset of hypertension in October 2020, where her blood pressure was 203/101 mmHg. After administration of nifedipine (30 mg/day), allisartan isoproxil (240 mg/day), and betaloc (47.5 mg/day), her blood pressure decreased to 140/70 mmHg, and she was discharged. However, her blood pressure was badly controlled, and her antihypertension medication regimen was changed several times under the guidance of her cardiologist. The latest regimen was norvasc amlodipine (5 mg/d), telmisartan (80 mg/day), and hydrochlorothiazide (12.5 mg/day). Her past medical history was unremarkable, there was no fever, chest pain, weight loss, skin lesions, or swollen lymph nodes. On admission, her blood pressure was 201/92 mmHg. Intravenous injection of sodium nitroprusside was administered at a dose of 4 μg/kg·min with a micropump. Physical examination revealed no other positive findings. Electrocardiogram showed sinus tachycardia. X-ray was normal. Laboratory testing demonstrated her erythrocyte sedimentation rate (29 mm/hour) was slightly above the normal value. Aldosterone, renin, adrenocorticotropic hormone, cortisol, angiotensin II, IgG4 were normal, but the patient had mild anemia (99 g/L). Since the patient had no hypertension before and there was no such family history, her elevated blood pressure was suspected to be a secondary hypertension related to renal artery stenosis. Blood pressure monitoring showed that her upper limb blood pressure was 175/87 mmHg, and her lower limb blood pressure was 125/72 mmHg. She was referred for aortic computed tomography angiography, which revealed a 6-cm soft tissue mass in the descending aorta with no contrast enhancement extending from the level of the superior margin of the eighth thoracic vertebra to the inferior margin of the tenth thoracic vertebra. The mass infiltrated the descending aortic wall and nearly occluded the aortic lumen (Figure 1). The presumptive diagnosis was angioleiomyosarcoma. Because the patient was suffering from uncontrollable hypertension resulting from severe stenosis of the descending aorta, mass resection surgery was planned.Download figureDownload PowerPointFigure 1. Computed tomography scan of the aorta showing the location and extension of the mass (white arrows) before the operation. A, Coronal view of the mass. B, Sagittal view of the mass. C, Axial view at the main pulmonary artery level. D, Three-dimensional reconstruction of the descending aorta showing severe stenosis of the lumen.Following left posterolateral thoracotomy and dissection, the mass was observed to abut the esophagus. Luckily, the mass did not infiltrate the esophagus, and it was dissected surgically from the surrounding tissue. After carefully exposing the normal aorta connected to the mass, the mass was surgically resected completely, followed by a descending aorta replacement using a polytetrafluoroethylene graft (Figure 2). The excised tumor specimen was firm, with white-brown resection surfaces and relatively well-defined borders. It was sent for pathological testing, where macroscopic examination revealed a solid tumor measuring ≈ 6 cm. The mass had infiltrated through the descending aortic wall and blocked most of the aortic lumen. Histological review showed infiltration by large histiocytes, lymphocytes, and plasma cells. Immunohistochemical staining demonstrated that the histiocytes were diffusely positive for CD163 and S100, focally positive for CD68, and negative for CD1a and langerin (Figure 3). Taken together, these findings suggested a diagnosis of Rosai-Dorfman disease. The patient's postoperative aortic computed tomography angiography before discharge showed good polytetrafluoroethylene graft patency (Figure S1). At the 6-month follow-up, the aortic computed tomography angiography result was fine (Figure S2), and her blood pressure had returned to normal without any medication.Download figureDownload PowerPointFigure 2. Intraoperative images. A, Gross specimen of the tumor showing the mass almost occluding the aortic lumen (red arrow). B, The tumor is excised, and the missing part of the descending aorta is replaced with a polytetrafluoroethylene graft (white arrow).Download figureDownload PowerPointFigure 3. Pathological specimens of the tumor. A, H&E staining of the excised specimen shows infiltration by large histiocytes, lymphocytes, and plasma cells (×100). Histiocytes marked with a red circle show mononuclear inflammatory cells in the cytoplasm. B, Histiocytes show positive immunoreactivity for S-100 (red arrows). C and D, CD68 and CD163 positive immunohistochemical staining (red arrows). E and F, Immunohistochemical staining shows negative results for langerin and CD1a.Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytic proliferation disease1 involving nodal and extranodal sites. According to the reports published, ≈ 43% of the RDD patients had extranodal site involvement.2 The disease mostly affects middle-aged females.3 Cardiovascular system involvement is rare, and no more than 30 patients cardiovascular RDD have been reported, Only a small number of reports retrieved from the literature have indicated that RDD involves the aorta. This patient had no nodal lesions, and the RDD was diagnosed postoperatively by pathological examination.The diagnosis of RDD is based on clinical symptoms, signs, imaging examination, and pathological findings. F-18 FDG PET/CT is valuable in both the initial evaluation and follow-up of RDD patients. The patient in this case was diagnosed postoperatively by histopathological examination, and she was referred for F-18 FDG PET/CT scanning when followed up; however, she did not undergo the examination for personal reasons. To distinguish RDD from other histiocytic disorders, histopathological examination results are needed. In typical RDD tissue samples, pathological features include histiocytic proliferation with emperipolesis and inflammatory cells infiltration, CD 68-, CD163-, and S100-positive staining, and CD1a- and langerin-negative staining.4 The findings in our case are consistent with these features.In summary, RDD involving the aorta is very rare. Preoperative diagnosis of RDD based on imaging results is challenging; thus, the pathological review of lesion specimens from is indispensable. Surgical treatment for RDD can be effective in most of the RDD patients if necessary, and the prognosis is often favorable after complete excision of the RDD mass.Article InformationSources of FundingDr Wang is supported by the National Natural Science Foundation of China (grant number 82070481).Supplemental MaterialFigures S1 and S2Disclosures None.FootnotesSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.122.014582For Sources of Funding and Disclosures, see page 293.Correspondence to: Zhiwei Wang, MD, Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No. 99, Zhangzhidong Rd, Wuchang District, Wuhan, China 430060. Email wangzhiwei@whu.edu.cnReferences1. Abla O, Jacobsen E, Picarsic J, Krenova Z, Jaffe R, Emile JF, Durham BH, Braier B, Charlotte F, Donadieu J., et al. Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease.Blood. 2018; 131:2877–2890. doi: 10.1182/blood-2018-03-839753CrossrefMedlineGoogle Scholar2. Summers MR, Pettersson G, Maalouf JF, Jaber WA. Sinus histiocytosis with massive lymphadenopathy: extra-nodal Rosai-Dorfman disease presenting as a rare aetiology of a large intracardiac mass.Eur Heart J. 2017; 38:1439–1440. doi: 10.1093/eurheartj/ehw409CrossrefMedlineGoogle Scholar3. Alruwaii ZI, Zhang Y, Larman T, Miller JA, Montgomery EA. Rosai-Dorfman disease of the digestive system - beware vasculopathy: a clinicopathologic analysis.Am J Surg Pathol. 2019; 43:1644–1652. doi: 10.1097/PAS.0000000000001343CrossrefMedlineGoogle Scholar4. Bruce-Brand C, Schneider JW, Schubert P. Rosai-Dorfman disease: an overview.J Clin Pathol. 2020; 73:697–705. doi: 10.1136/jclinpath-2020-206733CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails March 2023Vol 16, Issue 3 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014582PMID: 36943911 Originally publishedFebruary 8, 2023 Keywordsaortacomputed tomography angiographyhistiocytosis, sinushypertensionsurgeryPDF download Advertisement SubjectsAngiographyCardiovascular SurgeryComputerized Tomography (CT)HypertensionVascular Disease

Neointimal hyperplasia is a major clinical complication of coronary artery bypass graft and percutaneous coronary intervention. Smooth muscle cells (SMCs) play a vital roles in neointimal hyperplasia development and undergo complex phenotype switching. Previous studies have linked glucose transporter member 10(Glut10) to the phenotypic transformation of SMCs. In this research, we reported that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via promotion of mtDNA demethylation in SMCs. Glut10 is significantly downregulated in both human and mouse restenotic arteries. Global Glut10 deletion or SMC-specific Glut10 ablation in the carotid artery of mice accelerated neointimal hyperplasia, while Glut10 overexpression in the carotid artery triggered the opposite effects. All of these changes were accompanied by a significant increase in vascular SMCs migration and proliferation. Mechanistically, Glut10 is expressed primarily in the mitochondria after platelet-derived growth factor-BB (PDGF-BB) treatment. Glut10 ablation induced a reduction in ascorbic acid (VitC) concentrations in mitochondria and mitochondrial DNA (mtDNA) hypermethylation by decreasing the activity and expression of the Ten-eleven translocation (TET) protein family. We also observed that Glut10 deficiency aggravated mitochondrial dysfunction and decreased the adenosinetriphosphate (ATP) content and the oxygen consumption rate, which also caused SMCs to switch their phenotype from contractile to synthetic phenotype. Furthermore, mitochondria-specific TET family inhibition partially reversed these effects. These results suggested that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via the promotion of mtDNA demethylation in SMCs.

目的 比较Hybrid Ⅱ型杂交与全弓置换术治疗急性A型主动脉夹层合并脏器灌注不良的疗效.方法 2016 年 1 月～2020 年 1 月我院诊治的急性A型主动脉夹层合并脏器灌注不良病人 127 例,按手术方法不同分为两组,Hybrid组56 例,采用Hybrid Ⅱ型杂交手术,全弓置换组71 例,采用全弓置换术.结果 Hybrid Ⅱ组和全弓置换组术后呼吸机辅助时间分别为(32.6±26.7)小时和(61.8±31.1)小时,术后ICU住院时间分别为(75.3±30.6)小时和(104.4±34.1)小时,术后肾功能不全发生率分别为21.4%和 46.5%,术后 30 天内死亡率分别为 1.8%和 12.7%,术后 1 年内死亡率分别为5.4%和 18.3%,永久性神经功能损伤分别为 8.9%和 22.5%,两组比较,差异有统计学意义(P＜0.05).术后二次开胸止血、肝功能不全、气管切开、暂时性神经功能损伤、术后3 年内死亡率及内漏发生率比较,差异无统计学意义.结论 急性A型主动脉夹层合并脏器灌注不良病人,行Hybrid Ⅱ型杂交手术近期预后满意,远期预后有待进一步研究.

Background Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemia‒reperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model. Methods Hybrid nanoparticles composed of CaCO 3 /CaP/biotinylated-carboxymethylchitosan (CaCO 3 /CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation. Results CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation. Conclusions CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.

随着心脏移植手术技术逐步成熟、免疫抑制药广泛使用以及器官分配系统完善,供心来源不足已成为制约临床心脏移植发展的瓶颈,如何扩大供心来源是亟待解决的科学难题.近年,随着科学技术的发展以及新型技术的应用,移植界就如何扩大供心来源取得了许多突破性的进展,许多研究成果已逐步实现临床转化,推动了临床心脏移植的发展.因此,本文就扩大供心来源的最新技术及策略进行综述,重点探讨器官保存技术、边缘供心使用、异种移植、人工心脏以及生物人工心脏在缓解供心短缺中的作用,概述扩大供心来源当前所面临的挑战和未来方向,以期为临床心脏移植的进一步发展提供参考.