Atherosclerosis is a chronic inflammatory disease in which phenotypic and functional changes in vascular smooth muscle cells (VSMCs) contribute to vascular calcification and thrombosis. Specifically, VSMCs provide a significant
source of local thrombin generation in the vascular wall. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) protect against atherothrombotic events, but the underlying molecular mechanism is unknown. The aim of the present study was to establish the effects of n-3 PUFAs on thrombin generation at the surface of human VSMCs, and its implication in pro-calcifying inflammatory pathways. Administration of n-3 PUFAs to human VSMCs decreased thrombin generation without altering cell proliferation. Furthermore, the n-3 PUFA-mediated reduction in thrombin generation was a cellular
response unrelated to the expression of tissue factor and coagulation factors, but required exogenous prothrombin and activation of integrin αvβ3. Finally, the inhibition of thrombin generation by n-3 PUFAs was associated with reduced cleavage of osteopontin (OPN) into its pro-calcifying N-half fragment. These findings suggest that inhibitory effects of n-3 PUFA on VSMC thrombin generation and OPN cleavage may contribute to the beneficial cardiovascular effects of n-3 PUFAs.

03 - OMEGA-3 FATTY ACIDS INHIBIT THROMBIN FORMATION IN VASCULAR SMOOTH MUSCLE CELLS