Role of focal adhesions of vascular smooth muscle cells in thrombin generation - 06/01/20
Résumé |
Introduction |
Arterial stiffness is a major risk factor for several cardiovascular diseases. Extracellular matrix composition and cell matrix interactions at the level of focal adhesions (FAs) represent important mechanisms of vascular stiffness. The αvb3 integrin of vascular smooth muscle cells (VSMCs) is a major actor in cell-matrix interactions for migration, proliferation, adhesion but it is also involved in thrombin generation as a prothrombin receptor which plays a role in the coagulation cascade.
Objectives |
We hypothesized that different degrees of matrix stiffness can modify activation of FAs and the ability of VSMCs to support thrombin generation.
Methods |
Culture of human VSMCs (Lonza®) was performed on polyacrylamide hydrogel bound to the surface of cell culture wells with different matrix stiffnesses: 0.5, 4 and 50kPa.–Confocal microscopy was used for imaging intracellular structural proteins and activation of FAs (α-actin, focal adhesion kinase (FAK), talin1, vinculin, αvb3 integrin.)–Thrombin generation on VSMCs was assessed by a fluorometric assay.
Results |
Increase in matrix stiffness in the physiological range results in increased expression of α-actin and FAs size. Fluorescence intensities of FAs proteins (αvb3, talin1 and vinculin) was increased in 50kPa wells and this was associated with a higher phosphorylation of FAK. The endogenous thrombin potential (ETP) of VSMCs decreases with the increase in matrix stiffness (2155±39, 2038±35 and 1672±33nM/min at 0.5, 4 and 50kPa).
Conclusion |
Activation of FAs and actin polymerization depend on extracellular matrix stiffness. On a rigid matrix the involvement of αvb3 integrin in FA complex reduces its availability for the binding of prothrombin resulting in a decrease of thrombin generation on VSMCs. Finally, activation of the FA controls both arterial stiffness and the procoagulant properties of the vascular wall.
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Vol 12 - N° 1
P. 145 - janvier 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.