Department of Medical Physiology, Texas A & M University College of Medicine, Bryan, TX 77807, USA.
Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN 37232, USA.
Int J Mol Sci. 2022 Jun 14;23(12):6621. doi: 10.3390/ijms23126621.
Lymphedema and lipedema are complex diseases. While the external presentation of swollen legs in lower-extremity lymphedema and lipedema appear similar, current mechanistic understandings of these diseases indicate unique aspects of their underlying pathophysiology. They share certain clinical features, such as fluid (edema), fat (adipose expansion), and fibrosis (extracellular matrix remodeling). Yet, these diverge on their time course and known molecular regulators of pathophysiology and genetics. This divergence likely indicates a unique route leading to interstitial fluid accumulation and subsequent inflammation in lymphedema versus lipedema. Identifying disease mechanisms that are causal and which are merely indicative of the condition is far more explored in lymphedema than in lipedema. In primary lymphedema, discoveries of genetic mutations link molecular markers to mechanisms of lymphatic disease. Much work remains in this area towards better risk assessment of secondary lymphedema and the hopeful discovery of validated genetic diagnostics for lipedema. The purpose of this review is to expose the distinct and shared (i) clinical criteria and symptomatology, (ii) molecular regulators and pathophysiology, and (iii) genetic markers of lymphedema and lipedema to help inform future research in this field.
淋巴水肿和脂肪水肿是复杂的疾病。虽然下肢淋巴水肿和脂肪水肿肿胀的外在表现相似，但目前对这些疾病的机制理解表明了其潜在病理生理学的独特方面。它们具有某些共同的临床特征，如液体（水肿）、脂肪（脂肪扩张）和纤维化（细胞外基质重塑）。然而，它们在发病机制和遗传学的时间进程和已知分子调节剂方面存在差异。这种差异可能表明导致淋巴水肿和脂肪水肿间质液积聚和随后炎症的独特途径。与脂肪水肿相比，淋巴水肿中更深入地研究了导致疾病的因果机制和仅仅表明疾病状态的机制。在原发性淋巴水肿中，基因突变的发现将分子标志物与淋巴管疾病的机制联系起来。在这个领域仍有很多工作要做，以更好地评估继发性淋巴水肿的风险，并有望发现脂肪水肿的有效遗传诊断。本文的目的是揭示淋巴水肿和脂肪水肿的（i）独特和共同的临床标准和症状、（ii）分子调节剂和病理生理学以及（iii）遗传标志物，以帮助指导该领域的未来研究。
