Hepatic lymphatic vascular system in health and disease

Jeong, Jin Woo; Tanaka, Masanori; Iwakiri, Yasuko

doi:10.1016/j.jhep.2022.01.025

Cited by 31 publications

(38 citation statements)

References 149 publications

(162 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lymphatic vascular system is composed of lymphatic capillaries, also called initial lymphatics, and collecting lymphatic vessels [ 15 , 16 , 17 ]. In the liver, lymphatic vessels are located in three regions: portal, hepatic venous, and sub-capsular areas.…”

Section: The Lymphatic System In the Livermentioning

confidence: 99%

“…Portal lymphatic capillaries merge into collecting lymphatic vessels that are surrounded by contractile muscle cells and show continuous “zipper-like” junctions, like blood vessels. Hepatic collecting lymphatic vessels drain fluid into regional lymph nodes in the hepatic hilum [ 14 , 15 , 16 , 17 , 18 ]. From these nodes, lymphatic fluid continues to celiac lymph nodes, eventually draining into the cisterna chili at the lower end of the thoracic duct.…”

Section: The Lymphatic System In the Livermentioning

confidence: 99%

“…Hepatic venous capillaries run along the hepatic vein, merge into collecting vessels, and pass through the diaphragm, together with the inferior vena cava, to mediastinal lymph nodes. Lymphatic vessels underneath the liver capsule drain fluid into diaphragmatic lymph nodes in the thorax and eventually into mediastinal nodes [ 15 , 17 , 18 ].…”

Section: The Lymphatic System In the Livermentioning

confidence: 99%

“…Lymphatic capillaries consist of a single layer of lymphatic endothelial cells (LECs) without any smooth muscle cell/pericyte coverage. LECs have discontinuous “button-like” junctions, which efficiently regulate the entry of fluid, antigens, and immune cells into lymphatic capillaries [ 15 ]. Besides behaving as structural components of the lymphatic vessels, LECs actively drive the mobilization of immune cells and regulate their functions [ 15 ].…”

Section: The Lymphatic System In the Livermentioning

confidence: 99%

See 3 more Smart Citations

Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma

Cadamuro

Romanzi

Guido

et al. 2022

JPM

View full text Add to dashboard Cite

The prognosis of cholangiocarcinoma remains poor in spite of the advances in immunotherapy and molecular profiling, which has led to the identification of several targetable genetic alterations. Surgical procedures, including both liver resection and liver transplantation, still represent the treatment with the best curative potential, though the outcomes are significantly compromised by the early development of lymph node metastases. Progression of lymphatic metastasis from the primary tumor to tumor-draining lymph nodes is mediated by tumor-associated lymphangiogenesis, a topic largely overlooked until recently. Recent findings highlight tumor-associated lymphangiogenesis as paradigmatic of the role played by the tumor microenvironment in sustaining cholangiocarcinoma invasiveness and progression. This study reviews the current knowledge about the intercellular signaling and molecular mechanism of tumor-associated lymphangiogenesis in cholangiocarcinoma in the hope of identifying novel therapeutic targets to halt a process that often limits the success of the few available treatments.

show abstract

Section: The Lymphatic System In the Livermentioning

confidence: 99%

Section: The Lymphatic System In the Livermentioning

confidence: 99%

Section: The Lymphatic System In the Livermentioning

confidence: 99%

Section: The Lymphatic System In the Livermentioning

confidence: 99%

See 2 more Smart Citations

Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma

Cadamuro

Romanzi

Guido

et al. 2022

JPM

View full text Add to dashboard Cite

show abstract

“…In addition to the increased abundance of lymphatic vessels as a physiological compensation, the change in size of these vessels has been found in patients or animal models as a result of an increase in lymph production during advanced CLD [ 13 , 14 ]. While structural and functional changes in the lymphatic system have been studied in models of chronic liver disease, knowledge about the lymphatic network within the intestinal or mesenteric circulation and its function in the development of portal hypertension is limited [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Paneth Cells Regulate Lymphangiogenesis under Control of Microbial Signals during Experimental Portal Hypertension

et al. 2022

View full text Add to dashboard Cite

Intestinal microbiota can modulate portal hypertension through the regulation of the intestinal vasculature. We have recently demonstrated that bacterial antigens activate Paneth cells (PCs) to secrete products that regulate angiogenesis and portal hypertension. In the present work we hypothesized that Paneth cells regulate the development of lymphatic vessels under the control of intestinal microbiota during experimental portal hypertension. We used a mouse model of inducible PCs depletion (Math1Lox/LoxVilCreERT2) and performed partial portal vein ligation (PPVL) to induce portal hypertension. After 14 days, we performed mRNA sequencing and evaluated the expression of specific lymphangiogenic genes in small intestinal tissue. Intestinal and mesenteric lymphatic vessels proliferation was assessed by immunohistochemistry. Intestinal organoids with or without PCs were exposed to pathogen-associated molecular patterns, and conditioned media (CM) was used to stimulate human lymphatic endothelial cells (LECs). The lymphangiogenic activity of stimulated LECs was assessed by tube formation and wound healing assays. Secretome analysis of CM was performed using label-free proteomics quantification methods. Intestinal immune cell infiltration was evaluated by immunohistochemistry. We observed that the intestinal gene expression pattern was altered by the absence of PCs only in portal hypertensive mice. We found a decreased expression of specific lymphangiogenic genes in the absence of PCs during portal hypertension, resulting in a reduced proliferation of intestinal and mesenteric lymphatic vessels as compared to controls. In vitro analyses demonstrated that lymphatic tube formation and endothelial wound healing responses were reduced significantly in LECs treated with CM from organoids without PCs. Secretome analyses of CM revealed that PCs secrete proteins that are involved in lipid metabolism, cell growth and proliferation. Additionally, intestinal macrophages infiltrated the ileal mucosa and submucosa of mice with and without Paneth cells in response to portal hypertension. Our results suggest that intestinal microbiota signals stimulate Paneth cells to secrete factors that modulate the intestinal and mesenteric lymphatic vessels network during experimental portal hypertension.

show abstract

Evaluation of the definition of hyperdynamic circulation in patients with cirrhosis and ascites

et al. 2022

View full text Add to dashboard Cite

The aim of this study was to evaluate potential criteria for defining hyperdynamic circulation in patients with cirrhosis according to the severity of ascites and its association with the activation of vasoactive systems and markers of systemic inflammation. Cross‐sectional study of patients with cirrhosis and right heart catheter measurement from two different academic centers. We evaluated systemic vascular resistance (SVR)/cardiac output (CO) according to ascites severity. The first substudy evaluated the possible definition, the second validated the findings, and the third evaluated the possible mechanisms. Comparisons were performed by means of t test, Mann–Whitney U test, and analysis of variance. Finally, linear regression curves were adjusted to evaluate the relationship between CO and SVR according to the severity of ascites and compensated or decompensated stage of cirrhosis. The study included 721 patients (substudy 1, n = 437; substudy 2, n = 197; substudy 3, n = 87). Hyperdynamic circulation (HC), defined by absolute cutoffs, had no association with the presence or severity of ascites in the first two cohorts. No association was observed between HC with renin, aldosterone, or markers of bacterial translocation. Comparison of linear regression curves showed a shift of the CO–SVR relationship to the left in patients with refractory ascites (p < 0.001) compared to patients without ascites as well as to patients with decompensated cirrhosis (p = 0.002). Conclusion: HC according to the traditional concept of high CO and low SVR is not always present in ascites. Evaluation of the CO–SVR relationship according to the severity of ascites shows a shift to the left, suggesting that the presence of HC would be defined by this shift, independent of absolute values.

show abstract

Hepatic lymphatic vascular system in health and disease

Cited by 31 publications

References 149 publications

Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma

Translational Value of Tumor-Associated Lymphangiogenesis in Cholangiocarcinoma

Paneth Cells Regulate Lymphangiogenesis under Control of Microbial Signals during Experimental Portal Hypertension

Evaluation of the definition of hyperdynamic circulation in patients with cirrhosis and ascites

Contact Info

Product

Resources

About