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OBJECTIVES: To evaluate the presence of lipedema and lipedema-related factors in fibromyalgia patients. METHODS: The study included 100 female patients over the age of 18 who met the fibromyalgia diagnostic criteria. The patients were evaluated for the presence/stages of lipedema. The body mass index (BMI), waist-hip ratio, waist-height ratio, and presence of hematoma tendency/telangiectasias were recorded. Patients were asked to mark the severity of their pain (widespread/on lipedema) on a 10 cm visual analog scale (VAS). The ACR 2016 Fibromyalgia Diagnostic Criteria, The Beck Depression Inventory (BDI), and The Revised Fibromyalgia Impact Questionnaire were applied. RESULTS: Lipedema was observed in 50% of the patients (58% Stage 1 lipedema). In the lipedema group, age, duration of fibromyalgia diagnosis, hematoma tendency/presence of telangiectasias (for all; p < .001), menopausal status (p = .004), BDI score (p = .04), BMI (p = .02), history of medication for fibromyalgia (p = .01) were higher, and age at menarche (p = .01) was lower. Lipedema stage was moderately positively correlated with BMI, number of pregnancies (for both; r:0.53 p < .001) and waist-height ratio (r:0.43 p:0.002), while VAS-lipedema pain intensity was strongly positively correlated with VAS-widespread pain intensity (r:0.62 p < .001), and moderately positively correlated with symptom severity score (r:0.55 p < .001), BMI (r:0.54 p < .001), and fibromyalgia severity score (r:0.51 p < .001). Long fibromyalgia diagnosis time (p: 0.005), and low age at menarche (p: 0.05) were significant risk factors for the presence of lipedema. CONCLUSIONS: Lipedema is common in fibromyalgia patients. Long fibromyalgia diagnosis time and low age at menarche are significant risk factors for the presence of lipedema.

Lipedema, historically underrecognized, has recently gained attention due to advancements in research and growing public awareness. The Brazilian Consensus Statement on Lipedema, developed by the Brazilian Society of Angiology and Vascular Surgery, aims to establish clear recommendations for the diagnosis, treatment, and management of lipedema. Using the Delphi methodology, experts elaborated 90 statements about lipedema, which were then evaluated by a panel of 113 professionals. The statements were analyzed using SurveyMonkey, with a 75% agreement threshold required for their inclusion in the consensus statement. Most statements achieved significant consensus, with only 9 topics requiring further investigation. This consensus statement highlights the complexity of lipedema, the effectiveness of conservative treatment over surgery, the need for multidisciplinary approaches, and the importance of awareness to reduce underdiagnosis and stigma. It also underscores the ongoing need for research to develop more effective management strategies.

PURPOSE: To describe and analyse experiences of living with lipedema. Methods: Individual, semi-structured interviews with a purposive sample of 12 women diagnosed with lipedema and analysed by qualitative content analysis utilizing an inductive approach. RESULTS: The overarching theme, "An uncertain uphill battle against a divergent body and societal ignorance", covers the experiences of living with lipedema and is based on five categories; "Captivated by a disintegrating body", "Face the impairments of a chronic condition", "Experience social exclusion", "Need emotional support to go on" and "Mull over an insecure future". The women felt entrapped within their bodies and experienced social exclusion due to the chronic symptoms and the progressive body shape alteration caused by their illness. Having experienced deficient information on the illness, varying support from other people, and a deteriorating economic situation, the women face an uncertain future. CONCLUSIONS: Symptoms and restrictions caused by lipedema affect women's livelihood and future, as there are no indications for disease improvement. Preventive work aimed at reducing health deterioration should be a priority. More research is needed to raise healthcare awareness regarding difficulties experienced by patients with lipedema.

BACKGROUND: Ketosis seems to attenuate, or prevent, the rise in both ghrelin concentrations and subjective hunger ratings that follow weight loss. However, most of the previous studies have employed very-low energy diets (VLED) and are therefore limited in terms of generalizability. OBJECTIVES: To compare changes in ghrelin plasma concentrations after a low-carbohydrate (LCD) versus an isocaloric low-fat low energy diet (LED) in females with lipedema. Secondary objectives were to determine potential differences between diets in changes in satiety hormones, and subjective ratings of appetite. METHODS: Females with obesity and lipedema were randomized to either an LCD (75 g carbohydrates) or low-fat diet (180 g carbohydrates) for 8 weeks. Plasma concentrations of ghrelin, peptide YY, cholecystokinin (CCK), and glucagon-like peptide 1 (GLP-1), and subjective ratings of appetite were measured in the fasting and postprandial states, pre and post intervention. RESULTS: 55 females (30 in LCD) were included (age 47.9 ± 11.3 years, BMI 36.8 ± 5.1 kg/m2). Both LCD and low-fat groups lost weight (10.3 %, P < 0.001 and 7.3 %, P < 0.001, respectively), but the LCD lost significantly more. No within or between groups differences were found for ghrelin in the fasting state. A reduction in postprandial (tAUC) ghrelin was seen only in the LCD group (P = 0.002), and this change was significantly different from the low-fat group (P = 0.046). The LCD group also reported an increase in postprandial (both iAUC and tAUC) fullness ratings (P = 0.035 and P = 0.005, respectively), but this was not significantly different from the low-fat group (P = 0.703 and P = 0.365, respectively), despite the latter experiencing no change (P = 0.127 and P = 0.152, respectively). Conversely, only the low-fat group reported increased hunger in fasting (P = 0.046), but changes were not significantly different from the LCD group (P = 0.711). A decrease in postprandial (both tAUC and iAUC) CCK was observed in both LCD and low-fat diet groups (P ≤ 0.005 for all). CONCLUSION: Despite no changes in fasting ghrelin concentrations in either of the diet groups, a reduction in postprandial ghrelin and increased fullness was seen in the LCD group. These favorable changes in appetite in the LCD group might have contributed to the greater weight loss observed in this group. CLINICAL TRIAL REGISTRATION: NCT04632810, Effect of Ketosis on Pain and Quality of Life in Patients With Lipedema (Lipodiet).

Lipedema is a chronic disorder affecting women with a 10% incidence worldwide. It is often confused with obesity. This study was undertaken to study microRNAs in lipedema tissue assessed by direct hybridization using the robust n-counter flex DX CE-IVD platform. The mean age of the subjects participating in the study was 40.29 (±12.17). The mean body weight and BMI were 67.37 (±10.02) and 25.75 (±4.10), respectively. The lipedema stages included were I and II. The differential expressed human (hsa)-miRNAs were determined according to a log2 fold-change (LFC) of 0.5 and p value < 0.05. To these, increased expression of hsa-let-7g-5p was evident, as well as reduced levels of hsa-miR-371a-5p, -4454+7975, -365a+b-3p, -205-5p, -196a-5p, -4488, -2116-5p, -141-3p, -208a-3p, -302b-3p, 374a-5p, and -1297. Then, several bioinformatics tools were used to analyze microarray data focusing on validated target genes in silico. KEGG and Gene Ontology (GO) pathway enrichment analysis was conducted. Furthermore, the protein-protein interaction and co-expression network were analyzed using STRING and Cytoscape, respectively. The most upregulated miRNA mainly affected genes related to cell cycle, oocyte meiosis, and inflammatory bowel disease. The downregulated microRNAs were related to endocrine resistance, insulin resistance, hypersensitivity to AGE-RAGEs, and focal adhesion. Finally, we validated by RT-PCR the upregulated hsa-let-7g-5p and two down-regulated ones, hsa-miR-205-5p and hsa-miR-302b-3p, confirming microarray results. In addition, three mRNA target miRNAs were monitored, SMAD2, the target of the hsa-let-7g-5p, and ESR1 and VEGFA, the target of hsa-miR-205-5p and hsa-miR-302b-3p, respectively. Our results open a new direction for comprehending biochemical mechanisms related with the pathogenesis of lipedema, shedding light on this intricate pathophysiological condition that could bring to light possible biomarkers in the future.

The treatment of lipedema remains challenging, largely due to widespread misconceptions. Selecting the appropriate treatment method necessitates the use of accurate outcome measures. This study aims to evaluate the effectiveness of compression therapy combined with exercises versus exercises alone in lipedema patients using various outcome measures. Twenty-four women with lipedema were divided into two equal groups: one group received compression therapy plus exercises while the other group performed exercises only. The effectiveness of the treatment was assessed before and after the intervention using several measures: an SF-36 questionnaire, a symptom severity survey, circumference (via 3D scanning), and body composition analysis. Significant improvements were observed in the SF-36 Physical Functioning and SF-36 Energy/Fatigue scores among participants in the compression group. Additionally, there was a reduction in the heaviness of extremities, the disproportion between the trunk and limbs, and the level of swelling in the compression therapy. Circumferences decreased in both groups. Although more circumferences were significantly reduced in the compression group, the reduction at the point above the knee was greater in the non-compression group. Compression therapy is an effective treatment for lipedema. Various measures, such as quality-of-life questionnaires and symptom severity surveys, can be used as valuable tools for assessing the effectiveness of lipedema treatment.

Background: Lipedema is a disease characterized by an increase in extracellular fluid. In these patients, the increase in the amount of extracellular fluid may accelerate the progression of the disease. The aim of this study is to examine the effect of complex decongestive therapy (CDT) on intracellular/extracellular fluid balance. Methods and Results: Twenty-two female patients diagnosed with lipedema by a specialist lymphologist were included in the study. Patients were subjected to complex decongestive therapy and pneumatic compression therapy 6 days a week for 1 month. Extracellular and intracellular fluid volumes were assessed using bioimpedance spectroscopy before and after the treatment. A decrease in intracellular (p = 0.010) and extracellular (p = 0.002) fluid volumes was observed after the treatment. Conclusion: There is no completely curative treatment method for lipedema. Current treatments aim to slow down the progression of the disease. CDT is considered effective in reducing intracellular and extracellular fluid volume in lipedema patients. Therefore, it is thought to be effective in slowing down the progression of the disease.

BACKGROUND: Lipedema is a frequently misdiagnosed condition in women, often mistaken for obesity, which significantly deteriorates both quality of life and physical health. Recognizing the necessity for holistic treatment strategies, research has increasingly supported the integration of specific dietary approaches, particularly ketogenic diets focusing on low-carbohydrate and high-fat intake. OBJECTIVES: to evaluate the impact of ketogenic diets on women with lipedema through a systematic review and meta-analysis. METHODS: A systematic review and meta-analysis were conducted by reviewing published, peer-reviewed studies addressing the implications of a low-carbohydrate, high-fat (LCHF) ketogenic diet in managing lipedema following comprehensive scrutiny of digital medical databases, such as PubMed, PubMed Central, Science Direct, and the Web of Science. This research was governed by specified parameters, including an established search string composed of search terms and an eligibility criterion (PICO) as denoted by the principal authors. Statistical analysis was carried out using RevMan 5.4.1 software with the Newcastle-Ottawa Scale utilized for quality appraisal of the included studies. RESULTS: Seven studies reporting statistical outcomes were included in the systematic review and meta-analysis following a rigorous quality appraisal and data identification process. Three hundred and twenty-nine female participants were diagnosed with lipedema and treated using a low-carbohydrate, high-fat diet. Data analysis identified the high-fat diet with a mean study duration of 15.85 weeks. Mean Differences (MDs) on changes pre- and post-intervention showed significant reductions in BMI and total body weight [4.23 (95% CI 2.49, 5.97) p < 0.00001 and 7.94 (95% CI 5.45, 10.43) p < 0.00001 for BMI and body weight, respectively]. Other anthropometric measurements, such as changes in waist/hip circumferences and waist/hip ratios, showed a significant reduction in these parameters, with an MD of 8.05 (95% CI 4.66, 11.44) p < 0.00001 and an MD of 6.67 (95% CI 3.35, 9.99) p < 0.0001 for changes in waist and hip circumferences from baseline, respectively. Lastly, changes in pain sensitivity were statistically significant post-intervention [MD 1.12 (95% CI, 0.44, 1.79) p = 0.001]. All studies scored fair on the Newcastle-Ottawa Scale. CONCLUSIONS: despite the limited studies and low number of study participants, the review observed a significant reduction in anthropometric and body composition metrics, indicating a potentially beneficial association between LCHF ketogenic diets and lipedema management.

Gestrinone (R-2323), or ethylnorgestrienone, is a synthetic steroid of the 19-nortestosterone group more commonly used as an oral, intravaginal, or subcutaneous implant for the treatment of endometriosis, contraception, and estrogen-dependent conditions such as hypermenorrhea, premenstrual dysphoria, and intense menstrual cramps. This review aims to reevaluate the routes, doses, and applicability proposed for using gestrinone, including its use in new conditions such as menopause, lipedema, and sarcopenia. Here, we present the possible application of gestrinone as a long-acting therapeutic possibility through hormonal implants and the benefits and potential risks. Available evidence on the safety of doses and routes is limited. Gestrinone appears to be effective compared to other progestins and may have some advantages in the treatment of estrogen-dependent pathologies. Future research must evaluate gestrinone's long-term safety and potential therapeutic indications.

BACKGROUND: Lipoedema is a painful adipose tissue disorder, affecting the limbs of women, that is resistant to diet and exercise. The purpose of the study was to evaluate the retrospective health-related quality-of-life (HRQoL) outcomes for patients with lower limb lipoedema (LLL) following tumescent liposuction (TL). METHODS: Forty-seven patients received TL over 5 years from 2015-2020 for LLL. As part of their routine treatment evaluation, each patient completed 4 validated HRQoL questionnaires at initial assessment. The questionnaires examined the patients' experiences relating to anxiety and depression, lower extremity function, appearance, and symptoms. The same questionnaires were posted to the patients after an average of 12 months post-procedure/s to establish the outcomes of the intervention. RESULTS: The study demonstrated that patients' HRQoL improved at 12 months (average) following TL. The results of all the questionnaires were statistically significant, and patients with stage 3 LLL showed the most improvement in outcomes. CONCLUSION: The findings demonstrated that TL achieves positive HRQoL outcomes in patients with LLL; however, long-term follow-up is needed to determine if the benefits sustain. Additionally, larger prospective controlled studies are required to provide robust evidence for this procedure.

Body composition (BC) measured by DXA differs between devices. We aimed to compare regional and total BC measurements assessed by the Hologic Horizon A and the GE Lunar iDXA devices; to determine device-specific calibration equations for each BC parameter; and to assess the impact of this standardization procedure on the assessment of sarcopenia, lipedema, obesity, and cardiovascular risk with DXA. A total of 926 postmenopausal women (aged 72.9 ± 6.9 yr, height 160.3 ± 6.6 cm, weight 66.1 ± 12.7 kg) underwent BC assessment on each device within 1 h, following the ISCD guidelines. The included sample was split into 80% train and 20% test datasets stratified by age, height, and weight. Inter-device differences in BC parameters were assessed with Bland-Altman analysis, Pearson or Spearman correlation coefficients, and t-tests or Wilcoxon tests. The equations were developed in the train dataset using backward stepwise multiple linear regressions and were evaluated in the test dataset with the R-squared and mean absolute error. We compared the abovementioned BC-derived health conditions before and after standardization in the test set with respect to relative risk, accuracy, Kappa score, and McNemar tests. Total and regional body masses were similar (p>.05) between devices. BMC was greater for all regions in the Lunar device (p<.05), while fat and lean masses differed among regions. Regression equations showed high performance metrics in both datasets. The BC assessment from Hologic classified 2.13 times more sarcopenic cases (McNemar: p<.001), 1.39 times more lipedema (p<.001), 0.40 times less high cardiovascular risk (p<.001), and similarly classified obesity (p>.05), compared to Lunar. After standardization, the differences disappeared (p>.05), and the classification metrics improved. This study discusses how hardware and software differences impact BC assessments. The provided standardization equations address these issues and improve the agreement between devices. Future studies and disease definitions should consider these differences.

This S2k guideline was developed on the initiative and under the German Society of Phlebology and Lymphology (DGPL) leadership. The guideline aims to optimize the diagnosis and treatment of lipedema. It is intended to bring together the different approaches of the respective professional groups in a consensus-based manner and thus offer a basic concept for the best possible treatment of patients with lipedema. Sixty recommendations were formulated and agreed on in diagnostics, conservative and surgical treatment options, psychosocial factors and self-management. The guideline is intended to reflect the current scientific knowledge and be widely used for diagnosis and treatment recommendations for patients with lipedema. In particular, the guideline comments on diagnostic criteria, differential diagnoses, and coinciding clinical pictures, their influence on diagnosis and treatment, sensible treatment measures, and self-management options. The lipedema guideline summarizes the current national and international evidence and the German expert consensus and derives recommendations for the best treatment for patients with lipedema. The recommendations in the guideline are intended as an orientation aid in the sense of action and decision-making corridors from which deviations are possible in justified cases.

We evaluated the effect of compression leggings with micromassage in association with physical activity on women with lipedema, not previously treated and without recent changes in body weight. The treatment resulted in an improvement in all subjective parameters, in spontaneous and evoked pain, in the volume of the limbs, in the absence of significant changes in body weight, and regardless of the duration of use, age, years of illness, the clinical stage, and body mass index (BMI). Evoked pain did not improve in areas affected by untreated lipedema; foot circumferences did not increase. We found a significant reduction in the thickness of subcutaneous adipose tissue (SAT) and skin evaluated in multiple points of the lower limb. Micromassage compression leggings are proposed as an integral part of conservative treatment. A method is proposed for the clinical evaluation of evoked pain, called the Progressive Pain Check (PPC), which allows for the calculation of a numerical score called the Ricolfi-Patton Score (RPS) and for the ultrasound evaluation of tissues. The method is simple and repeatable and allows for completion of the clinical evaluation of the patient at diagnosis and for an evaluation of the effects of various treatments, even applied to just one side of the body.

PURPOSE OF REVIEW: This consensus statement from the Italian Society of Motor and Sports Sciences (Società Italiana di Scienze Motorie e Sportive, SISMeS) and the Italian Society of Phlebology (Società Italiana di Flebologia, SIF) provides the official view on the role of exercise as a non-pharmacological approach in lipedema. In detail, this consensus statement SISMeS - SIF aims to provide a comprehensive overview of lipedema, focusing, in particular, on the role played by physical exercise (PE) in the management of its clinical features. RECENT FINDINGS: Lipedema is a chronic disease characterized by abnormal fat accumulation. It is often misdiagnosed as obesity, despite presenting distinct pathological mechanisms. Indeed, recent evidence has reported differences in adipose tissue histology, metabolomic profiles, and gene polymorphisms associated with this condition, adding new pieces to the complex puzzle of lipedema pathophysiology. Although by definition lipedema is a condition resistant to diet and PE, the latter emerges for its key role in the management of lipedema, contributing to multiple benefits, including improvements in mitochondrial function, lymphatic drainage, and reduction of inflammation. Various types of exercise, such as aquatic exercises and strength training, have been shown to alleviate symptoms and improve the quality of life of patients with lipedema. However, standardized guidelines for PE prescription and long-term management of patients with lipedema are lacking, highlighting the need for recommendations and further research in this area in order to optimise therapeutic strategies.

Lymphedema and lipedema are chronic debilitating disorders that most commonly affect the upper and lower extremities. Although they can appear similar, they differ in important ways, which the authors of this article review and contrast.

BACKGROUND: Lipedema is the progressive symmetrical deposition of subcutaneous fat and fluid in the lower body, ordinarily sparing the trunk, upper limbs, face, and neck. It may follow an autosomal dominant inheritance pattern. The gold standard treatment for lipedema is complete decongestive therapy, consisting of manual lymphatic drainage and compression garments. This scoping review assessed the existing literature on the effectiveness of liposuction as an alternative treatment for lipedema. METHODS: A scoping review of electronically available literature within PubMed, Scopus, and Cochrane focused on liposuction as a treatment for lipedema considering the following inclusion criteria: human studies, case series of 10 or more, controlled trials, randomized controlled trials, patient-reported outcome measurement studies, survey analyses, descriptive studies, retrospective analyses, recurrence included, follow-up of 6 months or more, age 18 years or older, and treatment modality being liposuction. RESULTS: Thirteen studies were selected. Nine studies reported decreased compression therapy use among patients following liposuction. No studies reported a long-term increase in compression therapy following liposuction. Studies found self-reported improvements in pain, mobility, bruising, and overall quality of life for patients following liposuction, many of whom had previously been on compressive therapy. Studies reported low rates of serious adverse events following liposuction, including deep vein thrombosis, pulmonary embolism, and infection. CONCLUSIONS: These results suggest that liposuction can be a viable treatment alternative to compression therapy for lipedema in patients whose compression therapy has not been helpful. However, there is not enough evidence to say whether liposuction is as effective as compression for patients first presenting with lipedema.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

Background: Despite its increasing incidence and prevalence throughout Western countries, lipedema continues to be a very enigmatic disease, often misunderstood or misdiagnosed by the medical community and with an intrinsic pathology that is difficult to trace. The nature of lipedemic tissue is one of hypertrophic adipocytes and poor tissue turnover. So far, there are no identified pathways responsible, and little is known about the cell populations of lipedemic fat. Methods: Adipose tissue samples were collected from affected areas of both lipedema and healthy participants. For single-cell RNA sequencing analysis, the samples were dissociated into single-cell suspensions using enzymatic digestion and then encapsulated into nanoliter-sized droplets containing barcoded beads. Within each droplet, cellular mRNA was converted into complementary DNA. Complementary DNA molecules were then amplified for downstream analysis. Results: The single-cell RNA-sequencing analysis revealed three distinct adipocyte populations at play in lipedema. These populations have unique gene signatures which can be characterized as a lipid generating adipocyte, a disease catalyst adipocyte, and a lipedemic adipocyte. Conclusions: The single-cell RNA sequencing of lipedemic tissue samples highlights a triad of distinct adipocyte subpopulations, each characterized by unique gene signatures and functional roles. The interplay between these adipocyte subtypes offers promising insights into the complex pathophysiology of lipedema.

RATIONALE: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. OBJECTIVE: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. METHODS AND RESULTS: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. CONCLUSIONS: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.