Lymph flow regulates collecting lymphatic vessel maturation in vivo

Sweet, Daniel T.; Jiménez, Juan M.; Chang, Jeremy; Hess, Paul R.; Mericko-Ishizuka, Patricia; Fu, Jianxin; Xia, Lijun; Davies, Peter F.; Kahn, Mark L.

doi:10.1172/jci79386

Cited by 162 publications

(218 citation statements)

References 56 publications

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“…Another phenotype observed in Sdc4 −/− or Pecam1 −/− embryos was an increase in mural cell coverage in lymphatic vessels and this was even more pronounced in Sdc4 −/− ; Pecam1 −/− double nulls. These data support the existence of abnormal flow signaling in these mutants and are consistent with a previous report (Sweet et al, 2015). The enlarged lymphatic vessel diameter in Sdc4 −/− embryos has been linked with increased LEC proliferation.…”

Section: Discussionsupporting

confidence: 93%

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Wang¹,

Baeyens²,

Corti³

et al. 2016

Journal of Cell Science

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The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4 −/− ; Pecam1 −/− double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.

show abstract

Section: Discussionsupporting

confidence: 93%

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Wang¹,

Baeyens²,

Corti³

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…These data support the existence of abnormal flow signaling in these mutants and are consistent with a previous report (Sweet et al, 2015). The enlarged lymphatic vessel diameter in Sdc4 …”

Section: Discussionsupporting

confidence: 93%

“…A previous study has established that initiation of lymphatic fluid flow is required for the development of lymphatic valves, a process that involves the transcription factors Prox1 and FoxC2 (Sabine et al, 2012). Flow is also required for lymphatic fate maintenance (Chen et al, 2012), lymphatic collecting vessel maturation (Sweet et al, 2015) and lymphatic vessel stabilization (Sabine et al, 2015). Despite these data pointing to the role of fluid flow in lymphatic vasculature development, the molecular mechanisms involved in mechanotransduction in the lymphatic endothelium have not been established.…”

Section: Introductionmentioning

confidence: 99%

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

et al. 2016

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The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4 Pecam1−/− double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.

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“…[94][95][96][97] Mechanistically, FOXC2 cooperates with calcineurin/NFTAC1 transcription factor during the maturation of collecting lymphatic vessels. Several other molecules involved in the maturation of lymphatic vessels have been identified, including CX26, CX37, and CX43, 98 Reelin, 99 elastin microfibril interfacer 1 (EMILIN1), 100 109 ; these and the role of lymphatic flow-induced mechanotransduction 94,96,110 have recently been reviewed elsewhere. 7,111 Since the discovery of the first LEC-specific marker proteins ≈20 years ago, there has been a dramatic increase in our understanding of the molecular mechanisms involved in lymphatic vascular development.…”

Section: Maturation Of the Lymphatic Vascular Treementioning

confidence: 99%

Lymphatic System in Cardiovascular Medicine

Aspelund

Robciuc

Karaman³

et al. 2016

Circulation Research

273

258

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Abstract:The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

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Lymph flow regulates collecting lymphatic vessel maturation in vivo

Cited by 162 publications

References 56 publications

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development

Lymphatic System in Cardiovascular Medicine

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