BackgroundPrimary lymphedema (PLE) and kaposiform hemangioendothelioma-related lymphedema (KLE) are rare vascular anomalies (VAs). This study aimed to examine the clinical features, management, and prognosis of PLE and KLE.MethodThe clinical features, imaging, treatments, and outcomes of 12 patients with PLE and 12 patients with KLE were retrospectively reviewed.ResultsThe mean age at which signs/symptoms were diagnosed was 68.2 months for PLE patients and 25 months for KLE patients. In PLE, the involvement of multiple sites is common, whereas in KLE, it typically affects a single site. Morbid obesity, which is common in adult patients, is rare in pediatric PLE and KLE patients. Imaging agent accumulation was observed in KLE but not in PLE via lymphoscintigraphy. In contrast, complications of PLE primarily involve skin and soft tissue, whereas musculoskeletal system complications are more common in KLE. Regarding prognosis, most patients stabilize or even experience lesion regression after standard treatment.ConclusionPLE and KLE share clinical symptoms. PLE often involves multiple sites, whereas KLE typically presents unilaterally with local lymphatic stasis. Standardized treatment enables the majority of children with lymphedema to control the disease without progression, with KLE showing potential reversibility. Given their rarity, a multidisciplinary approach is crucial for diagnosis and management.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that typically presents in infancy or early childhood. As awareness of KHE increases, it is imperative that the management of KHE be updated to reflect the latest evidence-based guidelines. The aim of this study was to integrate the literature and Chinese expert opinions to provide updated recommendations that will guide the diagnosis, treatment, and prognosis of patients with KHE. According to this consensus statement, 28 nationally peer-recognized experts in vascular anomalies and an expert in evidence-based medicine were assembled and formed three consensus subgroups. A series of key themes and questions were developed for each group, including recommendations for diagnosis, treatment, and prognosis. A systematic search was conducted for English-language articles published in PubMed and other relevant studies identified by the expert panel. A diagnosis of KHE necessitates the integration of clinical, imaging, and histologic features. The treatment of KHE should be tailored to the specific characteristics of each patient, including the size of the lesion, the presence of symptoms, the location, and the overall condition of the patient. In addition to focusing on the disease itself, it is also important to consider the complications of KHE and their impact on prognosis. The recommendations presented herein are intended to assist in the guidance of clinical practice and decision-making in patients with KHE, with the objective of improving patient outcomes.

Objective: The diagnosis of abdominal lymphatic malformations (ALMs) is often overlooked in clinical practice. However, reports in the literature about ALMs are limited to case reports and series with small sample sizes. This study aimed to review our currently available data to describe the clinical characteristics of ALMs and evaluate the risk factors for acute abdomen caused by ALMs. Methods: We reviewed the records of patients with ALMs who were diagnosed between December 2008 and January 2023 in our institution. The associations between acute abdomen and ALMs were analyzed based on single-factor and multivariate logistic regression analyses. Results: This study included 345 patients with pathologically confirmed ALMs, with a slight female predominance of 1:1.4. Approximately 39.1% (135/345) of patients were asymptomatic, and 24.6% (85/345) presented with acute abdomen. Among the ALMs in the cohort, 42.6% (147/345) were retroperitoneal lymphatic malformations (LMs). The maximal lesion dimensions in patients with acute abdomen and nonacute abdomen were 10.0 cm and 7.8 cm, respectively, with no significant difference based on multivariate analyses. Children were more likely to develop acute abdomen than adults were (P = . 002: odds ratio, 5.128: 95% confidence interval, 1.835-14.326). ALMs accompanying acute abdomen were more common for lesions involving the small intestinal mesentery (P = . 023: odds ratio, 2.926: 95% confidence interval, 1.157-7.400). Conclusions: ALMs are rare with an insidious onset, and retroperitoneal LMs are the most common ALMs, followed by jejunal mesenteric LMs. Our retrospective analysis suggested that young age and small intestinal mesenteric lymphatic malformation are independent risk factors for acute abdomen with ALMs. (J Vasc Surg Venous Lymphat Disord 2025:13:101969.)

Hepatic hemangiomas can be classified into three morphologic patterns: focal (congenital hepatic hemangiomas [CHHs]), multifocal, and diffuse. We aimed to identify the clinical characteristics of CHH and evaluate the changes in CHH management at our institution over the last 2 decades. This was a retrospective cohort study of children diagnosed with CHH who were managed at 8 investigation sites. The primary outcome was changes in CHH size in patients at the last follow-up. The primary exposure of interest was management modality in 2 study periods (2003–2012 versus 2013–2022). Two hundred and eleven patients were analyzed. Four different subtypes of CHH were identified. Rapidly involuting CHH patients had complete involution/nearly complete involution, with a median age of 12.0 months. Noninvoluting CHH presented no change in CHH size. Partially involuting CHH patients presented with partial involution and had a stable tumor size at a median age of 16.0 months. Postnatally proliferating CHHs had an initial postnatal increase in CHH lesion size and underwent involution at a median age of 27.0 months. Further analysis revealed that management strategies for CHHs have shifted over time, with the proportion of patients receiving expectant management increasing from 35.4

To the Editor: Congenital hemangiomas are benign vascular tumors that differ from common infantile hemangiomas biologically and behaviorally.1 Several retrospective studies and case reports have reported the involuting pattern of rapidly involuting congenital hemangiomas (RICHs).2-5 However, no prospective studies reporting on the clinical features of RICH have been published. Although most RICHs are uncomplicated and can resolve spontaneously without causing morbidities, a significant minority of RICHs are associated with complications requiring timely referral to a specialist.

Kaposiform hemangioendotheliomas (KHEs) are vascular tumors that are considered borderline or locally aggressive and may lead to lethal outcomes. Traditional therapies, such as surgery and embolization, may be insufficient or technically impossible for patients with KHE. Sirolimus (or rapamycin), a specific inhibitor of mechanistic target of rapamycin, has recently been demonstrated to be very useful in the treatment of KHEs. Here, we highlight recent substantial progress regarding the effects of sirolimus on KHEs and discuss the potential mechanisms of action of sirolimus in treating this disease. The prevention of platelet activation and inflammation, along with antiangiogenic effects, the inhibition of lymphangiogenesis, the attenuation of fibrosis, or a combination of all these effects, may be responsible for the therapeutic effects of sirolimus. In addition, the mechanism of sirolimus resistance in some KHE patients is discussed. Finally, we review the somatic mutations that have recently been identified in KEH lesions, and discuss the potential of novel therapeutic targets based on these further understandings of the cellular and molecular pathogenesis of KHE.

Background: Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor that often occurs in infants and young children. The goal of this study was to analyze the clinical characteristics of KHE patients with bone destruction and provide clinical guidance for diagnosis and treatment. Methods: We conducted a descriptive cohort study with follow-up from January 2007 to January 2023 to collect demographic information and tumor-related clinical information from KHE patients with bone destruction. Results: A total of 269 KHE patients were included in the study, of whom 70 (26.0%) patients had tumors with bone destruction. The median age at diagnosis of patients with bone destruction was 19.0 months, which was much later than that of patients without bone destruction (P < 0.001). Patients with bone destruction were more likely to have a decreased range of motion (ROM) (P < 0.001). Metaphysis involvement was more likely to occur in the lower limb bones (P = 0.039), and the lower limb bones were more likely to be associated with decreased ROM (P = 0.001). Tumors involving extracompartmental bone were more likely to have decreased ROM (P = 0.003) and exhibit the Kasabach -Merritt phenomenon (P = 0.006). Conclusions: Based on the rarity and signi ficant heterogeneity of KHE patients with bone destruction, we should give full play to the role of multidisciplinary teams in addressing disease to reduce the long -term complications of KHE with bone destruction and improve the quality of life of patients. Type of Study: Prognostic Study. Level of Evidence: Level II. (c) 2023 Elsevier Inc. All rights reserved.

Infantile hemangioma (IH) is the most common benign tumor in infants and usually resolves on its own. However, a small portion of IH cases are accompanied by serious complications and other problems, impacting the physical and psychological health of the children affected. The pathogenesis of IH is highly controversial. Studies have shown that abnormal blood vessel formation is an important pathological basis for the development of IH. Compared with that in normal tissues, the equilibrium of blood vessel growth at the tumor site is disrupted, and interactions among other types of cells, such as immune cells, promote the rapid proliferation and migration of vascular tissue cells and the construction of vascular networks. Currently, propranolol is the most common systemic drug used to inhibit the growth of IHs and accelerate their regression. The purpose of this review is to provide the latest research on the mechanisms of angiogenesis in IH. We discuss the possible roles of three major factors, namely, estrogen, hypoxia, and inflammation, in the development of IH. Additionally, we summarize the key roles of tumor cell subpopulations, such as pericytes, in the proliferation and regression of IH considering evidence from the past few years, with an emphasis on the possible mechanisms of propranolol in the treatment of IH. Angiogenesis is an important event during the development of IH, and an in-depth understanding of the molecular mechanisms of angiogenesis will provide new insights into the biology and clinical treatment of IH.

Infantile hemangioma (IH) is the most common benign tumor in children. However, the exact pathogenesis of IH remains unclear. Integrated nontargeted and targeted metabolic analyses were performed to obtain insight into the possible pathogenic mechanism of IH. The results of nontargeted metabolic analysis showed that 216 and 128 differential metabolites (DMs) were identified between hemangioma-derived endothelial cells (HemECs) and HUVECs in positive-ion and negative-ion models, respectively. In both models, these DMs were predominantly enriched in pathways related to amino acid metabolism, including aminoacyl-tRNA biosynthesis and arginine and proline metabolism. Then, targeted metabolic analysis of amino acids was further performed to further clarify HemEC metabolism. A total of 22 amino acid metabolites were identified, among which only 16 metabolites, including glutamine, arginine and asparagine, were significantly differentially expressed between HemECs and HUVECs. These significant amino acids were significantly enriched in 10 metabolic pathways, including ‘alanine, aspartate and glutamate metabolism’, ‘arginine biosynthesis’, ‘arginine and proline metabolism’, and ‘glycine, serine and threonine metabolism’. The results of our study revealed that amino acid metabolism is involved in IH. Key differential amino acid metabolites, including glutamine, asparagine and arginine, may play an important role in regulating HemEC metabolism.

Objective:To analyze the clinical features, differential diagnosis, treatment and prognosis of complex lymphatic malformations.Methods:The clinical data of patients with complex lymphatic malformation were retrospectively analyzed from April 2010 to April 2022 in the Multidisciplinary Outpatient Department of the Vascular Disease Team of West China Hospital, Sichuan University. All patients were diagnosed with complex lymphatic malformation after consultation with multidisciplinary experts in pediatric surgery, radiology, plastic surgery, pathology, rehabilitation and other departments. The clinical manifestations, blood routine, coagulation function, magnetic resonance imaging and treatment methods of the patients were analyzed. According to the follow-up and disease results, the patients were divided into improvement, stability, progress and death.Results:A total of 18 patients with complex lymphatic malformations were included in the study, including 6 males and 12 females. The age of first diagnosis ranged from 1 month to 29 years old, and the median age was 2.5 years old. Patients were followed up and treated for 0.4 to 12.0 years, with an average follow-up of 3.5 years. Ten patients had pleural and pericardial effusion; 15 patients had visceral involvement which showed multifocal changes in imaging examinations; 9 cases were accompanied by bone destruction, which in Gorham-Stout disease patients broke through the cortex while in generalized lymphatic anomalies it did not; 14 patients had various degrees of coagulation abnormalities, of which 8 patients with severe coagulation dysfunction were all diagnosed as kaposiform lymphangiomatosis. Of the 18 patients, one kaposiform lymphangiomatosis patient died; six patients progressed; eight patients were stable; and three patients improved.Conclusion:The clinical characteristics of patients with complex lymphatic malformations are systemic, diverse and complex. The clinical symptoms of patients with diffuse lymphatic malformation accompanied by involvement of bone and multiple internal organs, chest and abdominal effusion, and coagulation dysfunction should be considered as complex lymphatic malformation. However, due to overlapping clinical characteristics of each subtypes, it is difficult to distinguish patients with complex lymphatic malformation, and the curative effect and prognosis are poor. Precision targeted drugs are the future research direction for the treatment of such diseases.

Objectives Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy.

Treatment with sirolimus, an inhibitor of the mammalian target of rapamycin pathway, has improved the prognosis of patients with kaposiform hemangioendothelioma (KHE). However, the efficacy, durability and tolerability of long-term sirolimus treatment in patients with KHE have not been well elucidated. We performed efficacy and safety assessments based on more than 4.5 years of follow-up in patients receiving sirolimus therapy for KHE. One hundred sixty-seven patients were analyzed, including 102 (61.1%) patients with the Kasabach-Merritt phenomenon (KMP). Follow-up was conducted after a median of 56.0 months. A total of 154 (92.2%) patients had a durable response to sirolimus treatment. No difference in durable response was found between patients without KMP and patients with KMP (95.4% vs 90.2%; difference, 5.2%; 95% confidence interval [CI], -4.0% to 13.1%). Rebound growth occurred in 17.3% of patients upon sirolimus discontinuation. Early treatment discontinuation (odds ratio [OR]: 3.103; 95% CI: 1.529-6.299; P = .002) and mixed lesion type (OR: 2.271; 95% CI: 0.901-5.727; P = .047) were associated with tumor rebound growth. No KHE-related deaths occurred in this cohort. At the last follow-up, approximately 17.4% of patients had active disease and/or changes in body structures to a variable extent. Serious adverse events occurred most commonly during the first year of sirolimus therapy. Follow-up of almost 4.5 years demonstrated that the efficacy of sirolimus persisted over time and that long-term treatment with sirolimus was not associated with unacceptable cumulative toxicities. However, nonresponse, tumor relapse and long-term sequelae remained challenges despite intensified and prolonged sirolimus therapy.

Background Infantile hemangioma (IH) is the most common tumor among infants, but the exact pathogenesis of IH is largely unknown. Our previous study revealed that glucose metabolism may play an important role in the pathogenesis of IH and that the inhibition of the glycolytic key enzyme phosphofructokinase-1 suppresses angiogenesis in IH. 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) is a metabolic enzyme that converts fructose-6-bisphosphate to fructose-2,6-bisphosphate (F-2,6-BP), which is the most potent allosteric activator of the rate-limiting enzyme phosphofructokinase-1. This study was performed to explore the role of PFKFB3 in IH.Methods Microarray analysis was performed to screen the differentially expressed genes (DEGs) between proliferating and involuting IH tissues. PFKFB3 expression was examined by western blot and immunohistochemistry analyses. Cell migration, apoptosis and tube formation were analyzed. Metabolic analyses were performed to investigate the effect of PFKFB3 inhibition by PFK15. Mouse models were established to examine the effect of PFKFB3 inhibition in vivo.Results PFKFB3 was identified as one of the most significant DEGs and was more highly expressed in proliferating IH tissues and hemangioma-derived endothelial cells (HemECs) than in involuting IH tissues and human umbilical vein endothelial cells, respectively. PFKFB3 inhibition by PFK15 suppressed HemEC glucose metabolism mainly by affecting glycolytic metabolite metabolism and decreasing the glycolytic flux. Moreover, PFK15 inhibited HemEC angiogenesis and migration and induced apoptosis via activation of the apoptosis pathway. Treatment with the combination of PFK15 with propranolol had a synergistic inhibitory effect on HemECs. Moreover, PFKFB3 knockdown markedly suppressed HemEC angiogenesis. Mechanistically, inhibition of PFKFB3 suppressed the PI3K-Akt signaling pathway and induced apoptotic cell death. More importantly, the suppression of PFKFB3 by PFK15 or shPFKFB3 led to markedly reduced tumor growth in vivo.Conclusions Our findings suggest that PFKFB3 inhibition can suppress IH angiogenesis and induce apoptosis. Thus, targeting PFKFB3 may be a novel therapeutic strategy for IH.

Infantile hemangioma (IH) is the most common benign tumor in children. Propranolol is the first-line treatment for IH, but the underlying mechanism of propranolol treatment in IH is not completely understood. Integrated transcriptional and metabolic analyses were performed to investigate the metabolic changes in hemangioma-derived endothelial cells (HemECs) after propranolol treatment. The findings were then further validated through independent cell experiments using a Seahorse XFp analyzer, Western blotting, immunohistochemistry and mitochondrial functional assays. Thirty-four differentially expressed metabolites, including the glycolysis metabolites glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-bisphosphate, were identified by targeted metabolomics. A KEGG pathway enrichment analysis showed that the disturbances in these metabolites were highly related to glucose metabolism-related pathways, including the pentose phosphate pathway, the Warburg effect, glycolysis and the citric acid cycle. Transcriptional analysis revealed that metabolism-related pathways, including glycine, serine and threonine metabolism, tyrosine metabolism, and glutathione metabolism, were highly enriched. Moreover, integration of the metabolomic and transcriptomic data revealed that glucose metabolism-related pathways, particularly glycolysis, were altered after propranolol treatment. Cell experiments demonstrated that HemECs exhibited higher levels of glycolysis than human umbilical vein ECs (HUVECs) and that propranolol suppressed glycolysis in HemECs. In conclusion, propranolol inhibited glucose metabolism in HemECs by suppressing glucose metabolic pathways, particularly glycolysis.

Sirolimus and everolimus have been widely used in children. These mammalian target of rapamycin (mTOR) inhibitors have shown excellent efficacy not only in organ transplant patients as immunosuppressive agents but also in patients with some other diseases. However, whether mTOR inhibitors can affect the growth and development of children is of great concern. In this study, using zebrafish models, we discovered that sirolimus and everolimus could slow the development of zebrafish, affecting indicators such as survival, hatching, deformities, body length, and movement. In addition to these basic indicators, sirolimus and everolimus had certain slowing effects on the growth and development of the nervous system, blood vessels, and the immune system. These effects were dose dependent. When the drug concentration reached or exceeded 0.5 μM, the impacts of sirolimus and everolimus were very significant. More interestingly, the impact was transient. Over time, the various manifestations of experimental embryos gradually approached those of control embryos. We also compared the effects of sirolimus and everolimus on zebrafish, and we revealed that there was no significant difference between these drugs in terms of their effects. In summary, the dose of sirolimus and everolimus in children should be strictly controlled, and the drug concentration should be monitored over time. Otherwise, drug overdosing may have a certain impact on the growth and development of children.

Introduction:Kaposiform lymphangiomatosis (KLA) is a rare and complex lymphatic anomaly with a poor prognosis. There is no standard treatment, and drug therapies are the most common therapeutic method. However, some patients' symptoms become gradually aggravated despite medical treatment. Splenectomy may be an alternative option when pharmacological therapies are ineffective.Materials and Methods:We reviewed and evaluated the cases of 3 patients with KLA who ultimately underwent splenectomy. Results: The lesions were diffusely distributed and involved the lungs and spleens of the 3 patients. Laboratory examinations revealed that all three patients had thrombocytopenia and reduced fibrinogen levels. All patients underwent symptomatic splenectomy after the medication failed. Surprisingly, their symptoms greatly improved. Histopathological investigation of the splenic lesions of the three patients confirmed the diagnosis of KLA. Immunohistochemical staining showed positivity for CD31, CD34, podoplanin, Prox-1 and angiopoietin 2 (Ang-2).Discussion:This study aimed to review the features of KLA patients treated by splenectomy and explore the underlying link between splenectomy and prognosis. The reason for the improvement after splenectomy may be related to increased Ang-2 levels and platelet activation in patients with KLA. Future research should seek to develop more targeted drugs based on molecular findings, which may give new hope for the treatment of KLA.

Abstract Introduction The Kasabach–Merritt phenomenon (KMP) is a severe complication of kaposiform hemangioendothelioma (KHE). The risk factors for KMP need further investigation. Methods The medical records of patients with KHE were reviewed. Univariate and multivariate logistic regression models were used for the risk factors for KMP, and the area under the receiver operator characteristic (ROC) curve was used to assess the predictive power of risk factors. Results A total of 338 patients with KHE were enrolled. The incidence of KMP was 45.9%. Age of onset (P < 0.001, odds ratio [OR] 0.939; 95% confidence interval [CI] 0.914–0.966), lesion size (P < 0.001, OR 1.944; 95% CI 1.646–2.296), mixed type (P = 0.030, OR 2.428; 95% CI 1.092–5.397), deep type (P = 0.010, OR 4.006; 95% CI 1.389–11.556), and mediastinal or retroperitoneal lesion location (P = 0.019, OR 11.864; 95% CI 1.497–94.003) were correlated with KMP occurrence through multivariate logistic regression. ROC curve analysis revealed that the optimal cutoffs were 4.75 months for the age of onset (P < 0.001, OR 7.206, 95% CI 4.073–12.749) and a lesion diameter of 5.35 cm (P < 0.001, OR 11.817, 95% CI 7.084–19.714). Bounded by a lesion size of 5.35 cm, we found significant differences in tumor morphology, age of onset, treatments, and hematological parameters. Using an onset age of 4.75 months as a cutoff, we found significant differences in tumor morphology, lesion size, hematological parameters, and prognosis. Conclusion For KHE patients with an onset age <4.75 months and/or lesion diameter >5.35 cm, clinicians should be wary of the occurrence of KMP. Active management is recommended to improve the prognosis.

目的研究糖酵解关键酶6-磷酸果糖-2-激酶/果糖-2, 6-二磷酸酶3(PFKFB3)对婴幼儿血管瘤(IH)内皮细胞(HemEC)生物活性的影响。方法收集4例增殖期及4例消退期IH组织, 从增殖期IH组织中提取原代HemEC, 以脐静脉内皮细胞(HUVEC)为对照。通过免疫组化与Western印迹法分别检测PFKFB3在IH组织与HemEC中的表达水平。采用CCK8实验检测0 ～ 10 μmol/L PFKFB3特异性抑制剂PFK15对HemEC细胞增殖的影响。体外培养HemEC, 采用5 μmol/L PFK15干预细胞, 采用Transwell法观察HemEC迁移能力, 流式细胞仪检测HemEC凋亡水平。组间比较采用t检验或方差分析。结果免疫组化显示, 增殖期IH组织中PFKFB3表达丰度(74.34% ± 5.26%)高于消退期(41.46% ± 2.99%, t = 9.40, P < 0.001)。Western印迹显示, HemEC中PFKFB3相对表达水平(0.73 ± 0.05)高于HUVEC(0.45 ± 0.04, t = 8.50, P < 0.001)。CCK8实验结果显示, 0.625、1.25、2.5、5、10 μmol/L PFK15组HemEC增殖活性均低于对照组(均P < 0.01)。Transwell实验显示, PFK15干预组HemEC迁移数(297 ± 15)低于对照组(422 ± 8, t = 12.59, P < 0.001)。流式细胞仪检测显示, PFK15干预组HemEC凋亡率(6.69% ± 0.64%)高于对照组(0.34% ± 0.07%, t = 17.07, P < 0.001)。结论糖酵解关键酶PFKFB3在IH增殖期组织与HemEC中高表达, PFKFB3抑制剂PFK15可抑制HemEC增殖、迁移并促进其凋亡。

Kaposiform hemangioendothelioma (KHE) is a rare borderline vascular tumor that usually presents as a mass of skin or deep soft tissue. We report a unique case of an 8-year-old KHE patient with bilateral symmetrical sites involving both femurs. The laboratory, radiographic, and pathological findings of the patient were minutely described. During the 6-month follow-up, the symptoms of pain and dysfunction of this patient were relieved. This study aimed to arouse clinicians’ concern about the symmetrical sites of KHE patients.

Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.