Rockson, S. G. Advances in lymphedema. Circ. Res. 128, 2003–2016 (2021).
Rockson, S. G. Lymphedema, inflammation, and fat. Lymphat. Res. Biol. 19, 115 (2021).
Oliver, G., Kipnis, J., Randolph, G. J. & Harvey, N. L. The lymphatic vasculature in the 21(st) century: novel functional roles in homeostasis and disease. Cell 182, 270–296 (2020).
Rockson, S. G. Lymphedema. Am. J. Med. 110, 288–295 (2001).
Witte, C. L. Pumps and lymphedema. Lymphology 34, 150–151 (2001).
Brorson, H., Ohlin, K., Olsson, G. & Karlsson, M. K. Breast cancer-related chronic arm lymphedema is associated with excess adipose and muscle tissue. Lymphat. Res. Biol. 7, 3–10 (2009).
Huang, L. H., Elvington, A. & Randolph, G. J. The role of the lymphatic system in cholesterol transport. Front. Pharmacol. 6, 182 (2015).
Martel, C. et al. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J. Clin. Invest. 123, 1571–1579 (2013).
Lim, H. Y. et al. Lymphatic vessels are essential for the removal of cholesterol from peripheral tissues by SR-BI-mediated transport of HDL. Cell Metab. 17, 671–684 (2013).
Burton, J. S., Sletten, A. C., Marsh, E., Wood, M. D. & Sacks, J. M. Adipose tissue in lymphedema: a central feature of pathology and target for pharmacologic therapy. Lymphat. Res. Biol. 21, 2–7 (2023).
Chen, S. X., Zhang, L. J. & Gallo, R. L. Dermal white adipose tissue: a newly recognized layer of skin innate defense. J. Invest. Dermatol. 139, 1002–1009 (2019).
Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46, 2347–2355 (2005).
Strissel, K. J. et al. Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56, 2910–2918 (2007).
Avraham, T. et al. Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema. FASEB J. 27, 1114–1126 (2013).
Ghaben, A. L. & Scherer, P. E. Adipogenesis and metabolic health. Nat. Rev. Mol. Cell Biol. 20, 242–258 (2019).
Sun, K., Kusminski, C. M. & Scherer, P. E. Adipose tissue remodeling and obesity. J. Clin. Invest. 121, 2094–2101 (2011).
Vasilenko, M. A. et al. The role of production of adipsin and leptin in the development of insulin resistance in patients with abdominal obesity. Dokl. Biochem. Biophys. 475, 271–276 (2017).
Prentice, K. J., Saksi, J. & Hotamisligil, G. S. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J. Lipid Res. 60, 734–740 (2019).
Schwartz, D. R. & Lazar, M. A. Human resistin: found in translation from mouse to man. Trends Endocrinol. Metab. 22, 259–265 (2011).
Hosogai, N. et al. Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56, 901–911 (2007).
Bambace, C. et al. Adiponectin gene expression and adipocyte diameter: a comparison between epicardial and subcutaneous adipose tissue in men. Cardiovasc. Pathol. 20, e153–e156 (2011).
Meyer, L. K., Ciaraldi, T. P., Henry, R. R., Wittgrove, A. C. & Phillips, S. A. Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity. Adipocyte 2, 217–226 (2013).
Kruth, H. S. Histochemical detection of esterified cholesterol within human atherosclerotic lesions using the fluorescent probe filipin. Atherosclerosis 51, 281–292 (1984).
Lim, H. Y. et al. Hypercholesterolemic mice exhibit lymphatic vessel dysfunction and degeneration. Am. J. Pathol. 175, 1328–1337 (2009).
Davis, M. J. et al. Multiple aspects of lymphatic dysfunction in an ApoE−/− mouse model of hypercholesterolemia. Front. Physiol. 13, 1098408 (2022).
Tall, A. R., Yvan-Charvet, L., Terasaka, N., Pagler, T. & Wang, N. HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 7, 365–375 (2008).
Rader, D. J., Alexander, E. T., Weibel, G. L., Billheimer, J. & Rothblat, G. H. The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. J. Lipid Res. 50, S189–S194 (2009).
Angeli, V. et al. Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 21, 561–574 (2004).
Cochran, B. J., Ong, K. L., Manandhar, B. & Rye, K. A. APOA1: a protein with multiple therapeutic functions. Curr. Atheroscler. Rep. 23, 11 (2021).
Bergt, C. et al. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Proc. Natl Acad. Sci. USA 101, 13032–13037 (2004).
Peng, D. Q. et al. Apolipoprotein A-I tryptophan substitution leads to resistance to myeloperoxidase-mediated loss of function. Arterioscler. Thromb. Vasc. Biol. 28, 2063–2070 (2008).
Atger, V. M. et al. Cyclodextrins as catalysts for the removal of cholesterol from macrophage foam cells. J. Clin. Invest. 99, 773–780 (1997).
Kritharides, L., Kus, M., Brown, A. J., Jessup, W. & Dean, R. T. Hydroxypropyl-β-cyclodextrin-mediated efflux of 7-ketocholesterol from macrophage foam cells. J. Biol. Chem. 271, 27450–27455 (1996).
Liu, S. M. et al. Cyclodextrins differentially mobilize free and esterified cholesterol from primary human foam cell macrophages. J. Lipid Res. 44, 1156–1166 (2003).
Zimmer, S. et al. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Sci. Transl. Med. 8, 333ra350 (2016).
Davies, B. & Morris, T. Physiological parameters in laboratory animals and humans. Pharm. Res. 10, 1093–1095 (1993).
Stella, V. J. & He, Q. Cyclodextrins. Toxicol. Pathol. 36, 30–42 (2008).
Jun, H. et al. Modified mouse models of chronic secondary lymphedema: tail and hind limb models. Ann. Vasc. Surg. 43, 288–295 (2017).
Weber, E. et al. Lymphatic collecting vessels in health and disease: a review of histopathological modifications in lymphedema. Lymphat. Res. Biol. 20, 468–477 (2022).
Oashi, K. et al. Pathophysiological characteristics of melanoma in-transit metastasis in a lymphedema mouse model. J. Invest. Dermatol. 133, 537–544 (2013).
Roh, K. et al. Therapeutic effects of hyaluronidase on acquired lymphedema using a newly developed mouse limb model. Exp. Biol. Med. 242, 584–592 (2017).
Ikomi, F. et al. Critical roles of VEGF-C-VEGF receptor 3 in reconnection of the collecting lymph vessels in mice. Microcirculation 15, 591–603 (2008).
Tassenoy, A. et al. Demonstration of tissue alterations by ultrasonography, magnetic resonance imaging and spectroscopy, and histology in breast cancer patients without lymphedema after axillary node dissection. Lymphology 39, 118–126 (2006).
Zhang, J., Hoffner, M. & Brorson, H. Adipocytes are larger in lymphedematous extremities than in controls. J. Plast. Surg. Hand. Surg. 56, 172–179 (2022).
Petrova, T. V. & Koh, G. Y. Biological functions of lymphatic vessels. Science 369, eaax4063 (2020).
Shimizu, Y. et al. Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema. J. Am. Heart Assoc. 2, e000438 (2013).
De Nardo, D. et al. High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat. Immunol. 15, 152–160 (2014).
Onishi, F. & Tan, B. K. Lymph node transfer using the middle jugular lymph node flap: anatomical study and a report of two cases. JPRAS Open 44, 430–440 (2025).
Tan, K. W. et al. Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D. Blood 122, 3666–3677 (2013).
Strand, K. et al. Subtype-specific surface proteins on adipose tissue macrophages and their association to obesity-induced insulin resistance. Front. Endocrinol. 13, 856530 (2022).
Wentworth, J. M. et al. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 59, 1648–1656 (2010).
Cochran, B. J. et al. Apolipoprotein A-I increases insulin secretion and production from pancreatic beta-cells via a G-protein–cAMP–PKA–FoxO1-dependent mechanism. Arterioscler. Thromb. Vasc. Biol. 34, 2261–2267 (2014).
Holm, S. A simple sequentially rejective multiple test procedure. Scand. J. Stat. 6, 65–70 (1979).
Krzywinski, M. & Altman, N. Points of significance: comparing samples-part I. Nat. Methods 11, 215–216 (2014).
