Lymphatic Collecting Vessel: New Perspectives on Mechanisms of Contractile Regulation and Potential Lymphatic Contractile Pathways to Target in Obesity and Metabolic Diseases.
Lymphatic Collecting Vessel: New Perspectives on Mechanisms of Contractile Regulation and Potential Lymphatic Contractile Pathways to Target in Obesity and Metabolic Diseases.
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DOI：
10.3389/fphar.2022.848088
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发表时间：
2022
影响因子：
5.6
通讯作者：
Muthuchamy M
中科院分区：
文献类型：
--
作者：
Lee Y;Zawieja SD;Muthuchamy M
肥胖和代谢综合征对心血管疾病的发展具有重要的风险，并且仍然是一个关键的医疗保健挑战。考虑到淋巴系统作为脂质吸收、免疫细胞运输、间质液和大分子稳态维持的联系，肥胖和代谢性疾病对淋巴功能的影响是淋巴研究的一个新兴领域。在过去的十年中，研究工作已经从肥胖表型与Prox1单倍功能不全的关联，以及肥胖作为淋巴水肿的危险因素的确定，到在多种代谢疾病模型和生物体中淋巴收集血管功能障碍的一致发现，以及肥胖症引起的病态肥胖淋巴水肿的特征。关键的是，最近的研究结果表明，淋巴功能的恢复也可以改善肥胖和胰岛素抵抗，假设淋巴靶向治疗是相关的药物干预措施。然而，我们对淋巴收集血管功能的理解仍然存在重大差距，特别是调节人类主动淋巴推进和淋巴返回所需的自发收缩活动的机制。在本文中，我们将回顾淋巴结构和收集血管功能的最新发现，包括淋巴肌收缩活动的离子基础的最新进展。然后，我们将讨论代谢破坏所观察到的淋巴功能障碍，以及用药物方法改善淋巴收集血管功能的潜在途径。
Obesity and metabolic syndrome pose a significant risk for developing cardiovascular disease and remain a critical healthcare challenge. Given the lymphatic system’s role as a nexus for lipid absorption, immune cell trafficking, interstitial fluid and macromolecule homeostasis maintenance, the impact of obesity and metabolic disease on lymphatic function is a burgeoning field in lymphatic research. Work over the past decade has progressed from the association of an obese phenotype with Prox1 haploinsufficiency and the identification of obesity as a risk factor for lymphedema to consistent findings of lymphatic collecting vessel dysfunction across multiple metabolic disease models and organisms and characterization of obesity-induced lymphedema in the morbidly obese. Critically, recent findings have suggested that restoration of lymphatic function can also ameliorate obesity and insulin resistance, positing lymphatic targeted therapies as relevant pharmacological interventions. There remain, however, significant gaps in our understanding of lymphatic collecting vessel function, particularly the mechanisms that regulate the spontaneous contractile activity required for active lymph propulsion and lymph return in humans. In this article, we will review the current findings on lymphatic architecture and collecting vessel function, including recent advances in the ionic basis of lymphatic muscle contractile activity. We will then discuss lymphatic dysfunction observed with metabolic disruption and potential pathways to target with pharmacological approaches to improve lymphatic collecting vessel function.
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影响因子：
20.1
作者：
Choi D;Park E;Jung E;Seong YJ;Hong M;Lee S;Burford J;Gyarmati G;Peti-Peterdi J;Srikanth S;Gwack Y;Koh CJ;Boriushkin E;Hamik A;Wong AK;Hong YK
通讯作者：
Hong YK
影响因子：
5.9
作者：
Bastías-Pérez M;Serra D;Herrero L
通讯作者：
Herrero L
影响因子：
4.5
作者：
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通讯作者：
Jaggar, Jonathan H.
DOI：
10.1152/ajpheart.00467.2015
发表时间：
2015-12-15
影响因子：
4.8
作者：
Chakraborty, Sanjukta;Zawieja, Scott D.;Muthuchamy, Mariappan
通讯作者：
Muthuchamy, Mariappan
影响因子：
3.7
作者：
Blum KS;Karaman S;Proulx ST;Ochsenbein AM;Luciani P;Leroux JC;Wolfrum C;Detmar M
通讯作者：
Detmar M