Simvastatin reverses multiple myeloma serum-induced prothrombotic phenotype in endothelial cells via ERK 1/2 signalling pathway

Abstract

: The introduction of new agents in multiple myeloma therapy has increased the overall response rate and improved clinical outcomes, but the increased risk of thrombotic complications impairs the quality of life of patient and the optimal thromboprophylaxis remains unknown. Increasing evidence has shown that statins can prevent venous thrombosis. Hence, we investigated the effects of simvastatin on multiple myeloma serum-related haemostatic imbalance in endothelial cells in vitro. The effects of simvastatin on procoagulant and anticoagulant protein expression were assessed on mixed multiple myeloma serum-treated human umbilical vein endothelial cells (HUVECs). The activity of these proteins was measured by thrombin generation and protein C activation assay. Then, the effects of extracellular signal-regulated kinase (ERK) 1/2 on endothelial activation were assessed by western blot and inhibition assay. We found that simvastatin inhibited multiple myeloma serum-induced expression of procoagulant protein tissue factor and phosphatidylserine and generation of thrombin on HUVECs. In contrast, simvastatin increased multiple myeloma serum-inhibited expression of anticoagulant protein endothelial protein C receptor and activation of protein C on HUVECs. Moreover, simvastatin reversed the multiple myeloma serum-induced prothrombotic phenotype, at least in part, via the inhibition of ERK 1/2 activation in endothelial cells. This study supports the beneficial effects of simvastatin on multiple myeloma serum-induced endothelial haemostatic imbalance, which suggests that simvastatin may serve as a new and appropriate antithrombotic approach for multiple myeloma patients.

Venous thromboembolism in multiple myeloma – choice of prophylaxis, role of direct oral anticoagulants and special considerations

“…Several disease‐related, treatment‐based and patient‐related factors can lead to thrombosis in myeloma (Bellotti et al , ; Amrani, ; O'Kane et al , ; Stirling et al , ; Mechtcheriakova et al , ; Yasin et al , ; Gado et al , ; Thiagarajan et al , ; Esmon, ; Yagci et al , ; Zangari et al , ; Palumbo et al , ; Elice et al , ; Auwerda et al , ; Kotlin et al , ; Dong et al , ; Guo et al , ). The effect of plasma cell neoplasms on thrombotic risk is paramount and the various ways they can promote clot formation are given in Table .…”

“…Conference abstracts have been included if deemed to be of particular relevance. Mechtcheriakova et al, 1999;Yasin et al, 1999;Gado et al, 2000;Thiagarajan et al, 2000;Esmon, 2001;Yagci et al, 2003;Zangari et al, 2003;Palumbo et al, 2004;Elice et al, 2006;Auwerda et al, 2007;Kotlin et al, 2008;Dong et al, 2018;Guo et al, 2018). The effect of plasma cell neoplasms on thrombotic risk is paramount and the various ways they can promote clot formation are given in Table I.…”

Προοπτική Μελέτη Των Παραγόντων Κινδύνου Και Των Μηχανισμών Της Πήξης Στις Πλασματοκυτταρικές Δυσκρασίες

“…• Single nucleotide polymorphisms (SNPs) and the NFκB1 gene (364) • Increased endothelial tissue factor expression (451) • Increased cell surface phosphatidylserine expression (451,452) • Changes in thrombin generation parameters (373,397) Myeloma Therapy Related There is an ever increasing need for RCTs designed to compare modes of The patient-profile, renal function, bleeding risk, frailty and preference should all be taken into account. Thromboprophylaxis should be administered for 4-6 months post treatment initiation or for as long as the patient is considered to be at risk of thrombosis.…”