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Emerging role of lymphatic vessels in reverse cholesterol transport.

Veronique A, Ying LH - Aging (Albany NY) (2013)

View Article: PubMed Central - PubMed

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Abnormal levels of cholesterol can have important cellular consequences and may lead to diseases such as atherosclerosis and type II diabetes... RCT is initiated when cells including macrophages efflux out the excess of cholesterol to prevent intracellular over-accumulation... Following cholesterol efflux, HDL-cholesterol is transported from the tissue back into the blood circulation... In contrast to the knowledge on the mechanisms by which cholesterol is effluxed out of the cells and its fate after reaching the liver, little information is available on how HDL-cholesterol travels from the peripheral tissues back to the blood circulation... The recent studies by Martel et al., and Lim et al., now provide convincing evidence for a role of lymphatic vessels in RCT... Indeed, impairment of lymphatic drainage induced by surgical excision in wild-type mice or naturally occurring in mice lacking the expression of one allele of vascular endothelial growth factor-C receptor significantly decreased the efficiency of RCT... Therefore, these new findings establish that lymphatic vessels tightly regulate RCT through the active transport of HDL-cholesterol... Interestingly, we showed previously that skin lymphatic vessels in these hypercholesterolemic mice exhibit structural defects which severely compromise their function... These observations suggest that the accumulation of cholesterol in arteries and skin from hyper-cholesterolemic mice may result from poor lymphatic drainage... Since these two genes regulate the structure and function of lymphatic vessels these findings support the hypothesis that defective lymphatic drainage may contribute to this lipid disorder... Massive lipid deposits are evident in the edematous tissues of patients with lymphedema and poor lymphatic drainage has been associated with the formation of xanthomas in humans... However, it remains to be determined whether RCT is affected in patients with lymphedema... Interestingly, the use of compression garments to resolve lymphedema ameliorate xanthomatous eruptions in patients.

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Lymphatic vessels are important for peripheral lipid clearance. Under normocholesterolemic conditions, functional lymphatic vessels regulate cholesterol transport from extra-hepatic tissues by contributing to RCT. Hypercholesterolemic conditions results in dysfunctional lymphatic vessels, which in turn can cause further cholesterol accumulation in tissues.
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Figure 1: Lymphatic vessels are important for peripheral lipid clearance. Under normocholesterolemic conditions, functional lymphatic vessels regulate cholesterol transport from extra-hepatic tissues by contributing to RCT. Hypercholesterolemic conditions results in dysfunctional lymphatic vessels, which in turn can cause further cholesterol accumulation in tissues.

Mentions: The relevance of these findings in humans is supported by clinical studies reporting a possible interconnection between lymphatic function and lipid accumulation in tissues (Figure 1). Patients with familial combined hyperlipidemia, a genetic dyslipidemia, which share similar clinical and biochemical features with type II diabetes mellitus, obesity and the metabolic syndrome showed decreased expression of FOXC2 and Prox-1 genes in their adipose tissue [7]. Since these two genes regulate the structure and function of lymphatic vessels these findings support the hypothesis that defective lymphatic drainage may contribute to this lipid disorder. Massive lipid deposits are evident in the edematous tissues of patients with lymphedema and poor lymphatic drainage has been associated with the formation of xanthomas in humans [8]. However, it remains to be determined whether RCT is affected in patients with lymphedema. Interestingly, the use of compression garments to resolve lymphedema ameliorate xanthomatous eruptions in patients [8]. Therefore, promoting efficient lymphatic drainage in lipid-related diseases including atherosclerosis and diabetes whose prevalence will continue to augment as a result of increase in aging population may be an attractive therapeutic intervention that deserves future investigations.


Emerging role of lymphatic vessels in reverse cholesterol transport.

Veronique A, Ying LH - Aging (Albany NY) (2013)

Lymphatic vessels are important for peripheral lipid clearance. Under normocholesterolemic conditions, functional lymphatic vessels regulate cholesterol transport from extra-hepatic tissues by contributing to RCT. Hypercholesterolemic conditions results in dysfunctional lymphatic vessels, which in turn can cause further cholesterol accumulation in tissues.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3824407&req=5

Figure 1: Lymphatic vessels are important for peripheral lipid clearance. Under normocholesterolemic conditions, functional lymphatic vessels regulate cholesterol transport from extra-hepatic tissues by contributing to RCT. Hypercholesterolemic conditions results in dysfunctional lymphatic vessels, which in turn can cause further cholesterol accumulation in tissues.
Mentions: The relevance of these findings in humans is supported by clinical studies reporting a possible interconnection between lymphatic function and lipid accumulation in tissues (Figure 1). Patients with familial combined hyperlipidemia, a genetic dyslipidemia, which share similar clinical and biochemical features with type II diabetes mellitus, obesity and the metabolic syndrome showed decreased expression of FOXC2 and Prox-1 genes in their adipose tissue [7]. Since these two genes regulate the structure and function of lymphatic vessels these findings support the hypothesis that defective lymphatic drainage may contribute to this lipid disorder. Massive lipid deposits are evident in the edematous tissues of patients with lymphedema and poor lymphatic drainage has been associated with the formation of xanthomas in humans [8]. However, it remains to be determined whether RCT is affected in patients with lymphedema. Interestingly, the use of compression garments to resolve lymphedema ameliorate xanthomatous eruptions in patients [8]. Therefore, promoting efficient lymphatic drainage in lipid-related diseases including atherosclerosis and diabetes whose prevalence will continue to augment as a result of increase in aging population may be an attractive therapeutic intervention that deserves future investigations.

View Article: PubMed Central - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Abnormal levels of cholesterol can have important cellular consequences and may lead to diseases such as atherosclerosis and type II diabetes... RCT is initiated when cells including macrophages efflux out the excess of cholesterol to prevent intracellular over-accumulation... Following cholesterol efflux, HDL-cholesterol is transported from the tissue back into the blood circulation... In contrast to the knowledge on the mechanisms by which cholesterol is effluxed out of the cells and its fate after reaching the liver, little information is available on how HDL-cholesterol travels from the peripheral tissues back to the blood circulation... The recent studies by Martel et al., and Lim et al., now provide convincing evidence for a role of lymphatic vessels in RCT... Indeed, impairment of lymphatic drainage induced by surgical excision in wild-type mice or naturally occurring in mice lacking the expression of one allele of vascular endothelial growth factor-C receptor significantly decreased the efficiency of RCT... Therefore, these new findings establish that lymphatic vessels tightly regulate RCT through the active transport of HDL-cholesterol... Interestingly, we showed previously that skin lymphatic vessels in these hypercholesterolemic mice exhibit structural defects which severely compromise their function... These observations suggest that the accumulation of cholesterol in arteries and skin from hyper-cholesterolemic mice may result from poor lymphatic drainage... Since these two genes regulate the structure and function of lymphatic vessels these findings support the hypothesis that defective lymphatic drainage may contribute to this lipid disorder... Massive lipid deposits are evident in the edematous tissues of patients with lymphedema and poor lymphatic drainage has been associated with the formation of xanthomas in humans... However, it remains to be determined whether RCT is affected in patients with lymphedema... Interestingly, the use of compression garments to resolve lymphedema ameliorate xanthomatous eruptions in patients.

Show MeSH
Related in: MedlinePlus