Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration

Tanaka, Hiroki; Yamamoto, Naoto; Suzuki, Minoru; Mano, Yoko; Sano, Masaki; Zaima, Nobuhiro; Sasaki, Takeshi; Setou, Mitsutoshi; Unno, Naoki

doi:10.3400/avd.oa.16-00122

Cited by 15 publications

(11 citation statements)

References 19 publications

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“…We have previously demonstrated that PCSK9 expressed by vascular smooth muscular cells in the aortic wall is related to the development of acute aortic dissection AAD , implicating PCSK9 in the loss of structural integrity of the aorta and subsequent imbalanced vasoconstriction. Current findings based on lipid molecular analysis have made a major contribution to the understanding of the pathogenesis of cardiovascular diseases 12,13 . Recently, the inhibition of PCSK9 through monoclonal antibodies has been indicated as a novel therapy for cardiovascular diseases 14 .…”

Section: Discussionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

et al. 2018

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Abdominal aortic aneurysm (AAA) is a common disease among the elderly. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been indicated as useful therapeutic tools for the treatment of cardiovascular diseases. The aim of this study was to elucidate the role of PCSK9 in the pathogenesis of AAA. We used fluorescence immunohistochemistry to assess the expression of PCSK9 in aortic tissues resected from 24 patients with AAA. Histological examination showed that PCSK9 expression in the adventitia region of the aneurysms was decreased in AAA samples. In the same region, the expression of CD36 increased. We hypothesized that CD36 expression might upregulate the transport of fatty acids into cells such as the adipocytes, and subsequently cause degradation of the adventitia in the aortic wall, contributing to AAA development.

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Section: Discussionmentioning

confidence: 99%

Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

et al. 2018

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“…Lymphatic injury in mouse models results in remodeling of adipose tissues and increased expression of adipocyte differentiation genes such as CCAAT/enhancer-binding proteinalpha (CEBP-α), adiponectin, peroxisome proliferator-activated receptor-gamma (PPAR-γ) (Rutkowski et al, 2010;Aschen et al, 2012;Zampell et al, 2012;Tashiro et al, 2017). Other experiments using a rat model in which collecting lymphatics are ligated have shown that insufficient lymphatic drainage results in abnormal lipid accumulation along the vein walls, causing chronic venous insufficiency (Tanaka et al, 2016). These findings are supported by in vitro experiments demonstrating that addition of lymphatic fluid (chylous fluid) to culture media of preadipocytes results in cellular differentiation, mature adipocyte gene expression (e.g., PPAR-γ, GLUT-4), and intracellular lipid accumulation (Harvey et al, 2005).…”

Section: Lymphatic Dysfunction Causes Adipose Deposition Lymphatic Flmentioning

confidence: 99%

Regulation of Lymphatic Function in Obesity

et al. 2020

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The lymphatic system has many functions, including macromolecules transport, fat absorption, regulation and modulation of adaptive immune responses, clearance of inflammatory cytokines, and cholesterol metabolism. Thus, it is evident that lymphatic function can play a key role in the regulation of a wide array of biologic phenomenon, and that physiologic changes that alter lymphatic function may have profound pathologic effects. Recent studies have shown that obesity can markedly impair lymphatic function. Obesity-induced pathologic changes in the lymphatic system result, at least in part, from the accumulation of inflammatory cells around lymphatic vessel leading to impaired lymphatic collecting vessel pumping capacity, leaky initial and collecting lymphatics, alterations in lymphatic endothelial cell (LEC) gene expression, and degradation of junctional proteins. These changes are important since impaired lymphatic function in obesity may contribute to the pathology of obesity in other organ systems in a feedforward manner by increasing low-grade tissue inflammation and the accumulation of inflammatory cytokines. More importantly, recent studies have suggested that interventions that inhibit inflammatory responses, either pharmacologically or by lifestyle modifications such as aerobic exercise and weight loss, improve lymphatic function and metabolic parameters in obese mice. The purpose of this review is to summarize the pathologic effects of obesity on the lymphatic system, the cellular mechanisms that regulate these responses, the effects of impaired lymphatic function on metabolic syndrome in obesity, and the interventions that may improve lymphatic function in obesity.

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“…Lymphatic stasis caused by venous hypertension leads to inflammation of the vein wall by inducing degeneration of adipocytes at that site. 16 This inflammation causes proliferation of medial smooth muscle cells and excessive production of fibrous matter, leading to hyperplasia, which in turn reduces the elastic compliance of the venous wall. 18,19 Therefore, structural deterioration of the microlymphatic network might contribute to venous insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Lymphatic flow restoration after stripping surgery for varicose veins: A case report

Yoshida

Koshima

Imai

et al. 2019

SAGE Open Medical Case Reports

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It has been suggested that the dynamics of the venous and lymphatic systems interact as a mutually dependent dual outflow system and that derangement of lymph flow could be reversed by surgical treatment of venous incompetence. In this report, we describe a patient in whom lymphatic function was restored after stripping of the great saphenous vein for varicosity. The patient was a 79-year-old woman who had varicose veins along the medial side of an edematous left leg. Lymphatic function was investigated using indocyanine green imaging to evaluate for the presence of lymphedema. Based on the findings, we made a diagnosis of bilateral varicosity of the great saphenous vein with left-sided lymphedema. The great saphenous vein was stripped between the groin and ankle on both sides. At 3 months after the stripping procedure, lymphatic flow was observed immediately after injection of indocyanine green in both legs along the medial side from the foot to the groin. We therefore determined that lymphatic flow had been restored after the stripping surgery. The functions of the venous and lymphatic systems are thought to be closely related, and that, if the function of one declines, the other will also be affected. Treatment of venous system, including stripping, may help to break the vicious cycle of lymphatic stasis and venous insufficiency.

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Insufficient Lymph Drainage Causes Abnormal Lipid Accumulation and Vein Wall Degeneration

Cited by 15 publications

References 19 publications

Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

Proprotein Convertase Subtilisin/Kexin Type 9 Is Associated with Degenerating Adipocytes in Abdominal Aortic Aneurysm

Regulation of Lymphatic Function in Obesity

Lymphatic flow restoration after stripping surgery for varicose veins: A case report

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