Endothelial Markers in Schistosomiasis Patients With or Without Portal Hypertension

Toledo, Carlos Fischer de; Carvente, Cláudia Teresa; Shigueoka, David Carlos; Borges, Durval Rosa

doi:10.1007/s10620-008-0475-8

Cited by 7 publications

(9 citation statements)

References 20 publications

(29 reference statements)

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“…In addition, portopulmonary hypertension is well documented (35)(36)(37). Although we did not measure portal venous pressure, elevated portal venous pressure has been reported previously in mice infected with S. mansoni (38)(39)(40) and is used as a diagnostic measure in patients with the hepatosplenic form of the disease (41).…”

Section: Discussionmentioning

confidence: 81%

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis

Crosby

Soon

Jones

et al. 2015

Am J Respir Crit Care Med

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Rationale: Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH.Objectives: To determine whether Bmpr2 1/2 mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling.Methods: Wild-type (WT) and Bmpr2 1/2 mice were infected percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right ventricular systolic pressure and liver and lung egg counts were measured. Serum, lung and liver cytokine, pulmonary vascular remodeling, and liver histology were assessed.Measurements and Main Results: By 17 weeks postinfection, there was a significant increase in pulmonary vascular remodeling in infected mice. This was greater in Bmpr2 1/2 mice and was associated with an increase in egg deposition and cytokine expression, which induced pulmonary arterial smooth muscle cell proliferation, in the lungs of these mice. Interestingly, Bmpr2 1/2 mice demonstrated dilatation of the hepatic central vein at baseline and postinfection, compared with WT. Bmpr2 1/2 mice also showed significant dilatation of the liver sinusoids and an increase in inflammatory cells surrounding the central hepatic vein, compared with WT. This is consistent with an increase in the transhepatic passage of eggs.Conclusions: This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2 1/2 mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis.

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Section: Discussionmentioning

confidence: 81%

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis

Crosby

Soon

Jones

et al. 2015

Am J Respir Crit Care Med

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“…Previous studies have demonstrated that the greater the portal blood flow the higher the levels of ALP and γGT, findings linked to possible anatomical changes in the biliary tree caused by fibrosis in the portal region [ 25 ]. Additionally, serum ALP is higher in schistosomiasis patients with portal hypertension than those without, although no differences are noted in γGT levels [ 26 ]. Hence, we conclude that our finding of high serum ALP is related to portal hypertension insofar as splenectomy reduces the portal flow, which in turn decreases ALP levels.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the reduction in direct bilirubin could reflect a better synthetic capacity of hepatocytes following the decrease of portal pressure in our splenectomized patients. Indeed, Toledo et al [ 26 ] also observed lower total and direct serum bilirubin in schistosomiasis patients without portal hypertension compared to those with.…”

Section: Discussionmentioning

confidence: 99%

Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

et al. 2015

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BackgroundSchistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients.Methodology/Principal FindingsForty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1.Conclusion/SignificanceThis study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status.

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“…However, this does not seem likely since aortic contraction induced by 10 nM ET-1 did not differ between groups. This finding is relevant since ET-1 can regulate pathophysiology of nonschistosomal portal hypertension (Ohara et al 2001, de Toledo et al 2009). In addition, Rho kinase inhibition reduced equally the contraction induced by ET-1 in both groups.…”

Section: Discussionmentioning

confidence: 96%

Schistosomiasis differentially affects vasoconstrictor responses: up-regulation of 5-HT receptor-mediated aorta contraction

Oliveira¹

2011

Mem. Inst. Oswaldo Cruz

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Schistosomiasis, classified by the World Health Organization as a neglected tropical disease, is an intravascular parasitic disease associated to a chronic inflammatory state. Evidence implicating inflammation in vascular dysfunction continues to mount, which, broadly defined, reflects a failure in the control of intracellular Ca2+ and consequently, vascular contraction. Therefore, we measured aorta contraction induced by 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1), two important regulators of vascular contraction. Isometric aortic contractions were determined in control and Schistosoma mansoni-infected mice. In the infected animals, 5-HT induced a 50% higher contraction in relation to controls and we also observed an increased contraction in response to Ca2+ mobilisation from sarcoplasmic reticulum. Nevertheless, Rho kinase inhibition reduced the contraction in response to 5-HT equally in both groups, discarding an increase of the contractile machinery sensitivity to Ca2+. Furthermore, no alteration was observed for contractions induced by ET-1 in both groups. Our data suggest that an immune-vascular interaction occurs in schistosomiasis, altering vascular contraction outside the mesenteric portal system. More importantly, it affects distinct intracellular signalling involved in aorta contraction, in this case increasing 5-HT receptor signalling

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Endothelial Markers in Schistosomiasis Patients With or Without Portal Hypertension

Abstract: In patients with schistosomiasis and portal hypertension (presinusoidal type), the levels of VEGF and ET-1 differ from those reported in patients with cirrhosis.

Cited by 7 publications

References 20 publications

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis

Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

Schistosomiasis differentially affects vasoconstrictor responses: up-regulation of 5-HT receptor-mediated aorta contraction

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Endothelial Markers in Schistosomiasis Patients With or Without Portal Hypertension

Abstract: In patients with schistosomiasis and portal hypertension (presinusoidal type), the levels of VEGF and ET-1 differ from those reported in patients with cirrhosis.

Cited by 7 publications

References 20 publications

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2+/− Mice with Schistosomiasis

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2+/− Mice with Schistosomiasis

Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

Schistosomiasis differentially affects vasoconstrictor responses: up-regulation of 5-HT receptor-mediated aorta contraction

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Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis

Hepatic Shunting of Eggs and Pulmonary Vascular Remodeling in Bmpr2^+/− Mice with Schistosomiasis