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Lipedema is a connective tissue disorder characterized by increased dilated blood vessels (angiogenesis), inflammation, and fibrosis of the subcutaneous adipose tissue. This project aims to gain insights into the angiogenic processes in lipedema using human umbilical vein endothelial cells (HUVECs) as an in vitro model. HUVECs were cultured in conditioned media (CM) collected from healthy (non-lipedema, AQH) and lipedema adipocytes (AQL). The impacts on the expression levels of multiple endothelial and angiogenic markers [CD31, von Willebrand Factor (vWF), angiopoietin 2 (ANG2), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMPs), NOTCH and its ligands] in HUVECs were investigated. The data demonstrate an increased expression of CD31 and ANG2 at both the gene and protein levels in HUVECs treated with AQL CM in 2D monolayer and 3D cultures compared to untreated cells. Furthermore, the expression of the vWF, NOTCH 4, and DELTA-4 genes decreased. In contrast, increased VEGF, MMP9, and HGF gene expression was detected in HUVECs treated with AQL CM cultured in a 2D monolayer. In addition, the results of a tube formation assay indicate that the number of formed tubes increased in lipedema-treated HUVECs cultured in a 2D monolayer. Together, the data indicate that lipedema adipocyte-CM promotes angiogenesis through paracrine-driven mechanisms.
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BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.
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- Lipedema (2)
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