Expression profile of haemostasis genes in vascular wall: is internal jugular vein protected from thrombosis in impaired outflow condition?

Background: Outflow disturbance in patients with internal jugular vein (IJV) abnormalities has been widely assessed through morphological and functional evaluation, and associated with clinical symptoms and demyelination changes. Variations of haemostasis gene expression have been reported in response to stimuli mimicking the forces exerted by blood on the vessel wall, and to flow properties. Expression patterns of haemostasis genes associated with impaired IJV outflow have never been investigated nor compared with those of other veins. Methods: The morphological characterization and flow disturbance assessment of IJV was conducted in four patients with multiple sclerosis by high resolution Doppler ultrasound and magnetic resonance venography.To assess differences in expression patterns, a microarray-based transcriptome analysis was performed in wall specimens from IJV and saphenous veins (SV), collected during surgical reconstruction of IJV by patch angioplasty. Results: The transcriptome analysis revealed 3375 differentially expressed transcripts/genes (1642 up- and 1733 down regulated) between IJV and SV wall (≥2 fold change, multiple testing correction P<0.05). Among the up regulated genes, the most significant enrichment was observed for processes related to inflammatory response (P=8.0E-19). Noticeably, the pathway “complement and coagulation cascades” also showed significant up regulation (P<1.0E-4). In this pathway, several significant differences were observed for genes expressed in endothelium and inhibiting the tissue factor pathway (TFPI, P=0.0005), and acting within the activated protein C pathway (PROS1, P=0.0005; THBD, P=0.0045; PROCR, P=0.0175). The fibrinolytic pathway also appeared to be potentiated (up regulation of PLAT, P=0.0003 and PLAUR, P=0.0030; down regulation of SERPINE1, P=0.0014). Conclusions: The increased expression of anticoagulant and profibrinolytic components would originate thromboprotective IJV wall features in response to flow stasis/disturbance, a potentially prothrombotic condition. The parallel up-regulation of genes encoding anticoagulant/anti-inflammatory proteins (EPCR, TM, PS, TFPI), and of a number of pro-inflammatory genes depicts a delicate balance in IJV with outflow disturbance.