harten.PNG

Lead Investigator: Ingrid A. Harten, PhD

Institution: Benaroya Research Institute at Virginia Mason

LF Funding History: 2017 Proof of Concept Award

Hypothesis: To determine whether the amounts of hyaluronan and its binding partners in tissues of lipedema patients correlate with disease severity.

Current LF Collaborations: This research will be carried out in collaboration with Dr. Karen Herbst and the TREAT Program at the University of Arizona, with the goal of characterizing the extracellular matrix (ECM) components, hyaluronan (HA) and its molecular partners, in human lipedema and control fat tissues.

Collaborative Opportunities: Additional collaborations are desired within the medical community to increase access to lipedema patients in the Seattle Area. Collaborations are also sought to strenghten general understanding of ECM in subcutaneous adipose biology and adipose tissue lymphatics.

Project: An In-depth Analysis of Hyaluronan in the Extracellular Matrix of Adipose Tissue in Lipedema

Although the cause of lipedema is currently unknown, it is thought that the extracellular matrix (ECM), the support system around the cells, is a primary player in this disease. In particular, an ECM molecule called hyaluronan (HA) has been shown to promote fat cell growth, fat tissue inflammation, and the buildup of collagen surrounding fat cells, called fibrosis, all of which are known as features of lipedema. Dr. Harten's research focuses on elucidating the involvement of HA and its binding partner, the chondroitin sulfate proteoglycan, versican, in modulating the inflammatory response and the development of fibrosis in a variety of tissues including fat.

In this study, histological analyses of lipedema fat tissue will be undertaken to determine if HA and its molecular partners, such as versican, are present in abnormal amounts in lipedema tissue, in comparison with normal fat tissue from age- and BMI-matched individuals. High levels of these molecules will indicate a direct role for ECM in the disease process and identify HA as a potential therapeutic target.

Omental adipose tissue from mice lacking LDL receptor and fed a diabetagenic diet, stained for general ECM composition with Movat's Pentachrome (blue = glycosaminglycans, red = cytosol, purple = nuclei, black elastin, and yellow = collagen), HA is stained specifically with an affinity probe and macrophages with Mac2 antibody (adapted from Han CY et al. Diabetes 56, 22600-2273, 2007).

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