Nicole Ziliotto1, Silvia Meneghetti1, Erica Menegatti2, Marcello Baroni1, Barbara Lunghi1, Fabrizio Salvi3, Manuela Ferracin4, Alessio Branchini1, Donato Gemmati5, Francesco Mascoli6, Paolo Zamboni2, Francesco Bernardi7, Giovanna Marchetti5. 1. Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy. 2. Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Italy. 3. Center for Immunological and Rare Neurological Diseases, Bellaria Hospital, IRCCS of Neurological Sciences, Bologna, Italy. 4. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. 5. Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy. 6. Unit of Vascular and Endovascular Surgery, S. Anna University-Hospital, Ferrara, Ferrara, Italy. 7. Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy. Electronic address: ber@unife.it.
Abstract
INTRODUCTION: Venous bed specificity could contribute to differential vulnerability to thrombus formation, and is potentially reflected in mRNA profiles. MATERIALS AND METHODS: Microarray-based transcriptome analysis in wall and valve specimens from internal jugular (IJV) and saphenous (SV) veins collected during IJV surgical reconstruction in patients with impaired brain outflow. Multiplex antigenic assay in paired jugular and peripheral plasma samples. RESULTS: Most of the top differentially expressed transcripts have been previously associated with both vascular and neurological disorders. Large expression differences of HOX genes, organ patterning regulators, pinpointed the vein positional identity. The "complement and coagulation cascade" emerged among 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. The jugular plasma levels of several proteins, encoded by differentially expressed genes, 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.
INTRODUCTION: Venous bed specificity could contribute to differential vulnerability to thrombus formation, and is potentially reflected in mRNA profiles. MATERIALS AND METHODS: Microarray-based transcriptome analysis in wall and valve specimens from internal jugular (IJV) and saphenous (SV) veins collected during IJV surgical reconstruction in patients with impaired brain outflow. Multiplex antigenic assay in paired jugular and peripheral plasma samples. RESULTS: Most of the top differentially expressed transcripts have been previously associated with both vascular and neurological disorders. Large expression differences of HOX genes, organ patterning regulators, pinpointed the vein positional identity. The "complement and coagulation cascade" emerged among 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. The jugular plasma levels of several proteins, encoded by differentially expressed genes, 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.
Authors: Iguaracy Pinheiro-de-Sousa; Miriam H Fonseca-Alaniz; Samantha K Teixeira; Mariliza V Rodrigues; Jose E Krieger Journal: Sci Rep Date: 2022-01-25 Impact factor: 4.379