Background: The ample heterogeneity of veins, related to their specific role and position should modulate the transcriptional profile of anticoagulants and procoagulant genes which contribute to the “in situ” hemostasis balance, and could modulate the ability of the individual vascular bed to counteract prothrombotic stimuli. The internal jugular vein (IJV) has a major role in cerebral venous return towards the heart, and differs from saphenous vein (SV) for morphological and hemodynamic characteristics. Aims: To compare the IJV and SV transcriptomes, which could participate in venous bed specificity and vulnerability to thrombus formation. Methods: Microarray-based transcriptome analysis in wall and valve specimens from IJV and SV collected during surgical reconstruction of IJV by patch angioplasty in multiple sclerosis patients with impaired brain outflow. Multiplex antigenic assay in paired jugular and peripheral plasma samples. Results: 3375 differentially expressed transcripts in walls defined distinct venous expression profiles. The “complement and coagulation cascade” emerged among the enriched pathways. In IJV, upregulation of genes for coagulation inhibitors (TFPI, PROS1), activated protein C pathway receptors (THBD, PROCR), fibrinolysis activators (PLAT, PLAUR), and downregulation of the fibrinolysis inhibitor (SERPINE1) and of contact/amplification pathway genes (F11, F12), would be compatible with a thromboprotective profile in respect to SV. Further, in SV valve the prothrombinase complex genes (F5, F2) were up-regulated and the VWF showed the highest expression. Differential expression of several VWF regulators (ABO, ST3GAL4, SCARA5, CLEC4M) was also observed. Among other differentially expressed hemostasis-related genes, heparanase (HPSE)/heparanase inhibitor (HPSE2) were up-/down-regulated in IJV, which might support procoagulant features and disease conditions. For several proteins, encoded by differentially expressed genes, the jugular plasma levels were lower and highly correlated with peripheral levels. Conclusions: The IJV and SV rely on differential expression of many hemostasis and hemostasis-related genes to balance local hemostasis, potentially related to differences in vulnerability to thrombosis

Expression profiles of the internal jugular and saphenous veins: focus on hemostasis genes

Ziliotto N
Primo
;
2020-01-01

Abstract

Background: The ample heterogeneity of veins, related to their specific role and position should modulate the transcriptional profile of anticoagulants and procoagulant genes which contribute to the “in situ” hemostasis balance, and could modulate the ability of the individual vascular bed to counteract prothrombotic stimuli. The internal jugular vein (IJV) has a major role in cerebral venous return towards the heart, and differs from saphenous vein (SV) for morphological and hemodynamic characteristics. Aims: To compare the IJV and SV transcriptomes, which could participate in venous bed specificity and vulnerability to thrombus formation. Methods: Microarray-based transcriptome analysis in wall and valve specimens from IJV and SV collected during surgical reconstruction of IJV by patch angioplasty in multiple sclerosis patients with impaired brain outflow. Multiplex antigenic assay in paired jugular and peripheral plasma samples. Results: 3375 differentially expressed transcripts in walls defined distinct venous expression profiles. The “complement and coagulation cascade” emerged among the enriched pathways. In IJV, upregulation of genes for coagulation inhibitors (TFPI, PROS1), activated protein C pathway receptors (THBD, PROCR), fibrinolysis activators (PLAT, PLAUR), and downregulation of the fibrinolysis inhibitor (SERPINE1) and of contact/amplification pathway genes (F11, F12), would be compatible with a thromboprotective profile in respect to SV. Further, in SV valve the prothrombinase complex genes (F5, F2) were up-regulated and the VWF showed the highest expression. Differential expression of several VWF regulators (ABO, ST3GAL4, SCARA5, CLEC4M) was also observed. Among other differentially expressed hemostasis-related genes, heparanase (HPSE)/heparanase inhibitor (HPSE2) were up-/down-regulated in IJV, which might support procoagulant features and disease conditions. For several proteins, encoded by differentially expressed genes, the jugular plasma levels were lower and highly correlated with peripheral levels. Conclusions: The IJV and SV rely on differential expression of many hemostasis and hemostasis-related genes to balance local hemostasis, potentially related to differences in vulnerability to thrombosis
2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1140982
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