BACKGROUND: -Although disturbed flow is thought to play a central role in the development of advanced @entity453 , no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap @entity1856 (TCFA). METHODS AND RESULTS: - @entity39751 - @entity756 hypercholesterolemic minipigs (N=5) were instrumented with an intracoronary @entity3517 ( @entity3517 ). Frequency-domain optical coherence tomography was obtained at baseline, immediately post-stent, 19, and 34 weeks and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially-collected histological sections and co-registered to the distribution of each shear metric. The @entity3517 caused a flow-limiting @entity850 and blood flow exiting the @entity3517 caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ~3-fold higher downstream of the @entity3517 compared to both upstream of the @entity3517 and in the control artery (p<0.001). @entity1442 were also primarily observed downstream of the @entity3517 , in locations initially exposed to both low (p<0.002) and multidirectional (p<0.002) shear stress. TCFA regions demonstrated significantly lower shear stress that persisted over the duration of the study compared to other plaque types (p<0.005). CONCLUSIONS: -These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced @entity453 . Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of TCFA.

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in XXXX - @entity756 Hypercholesterolemic Minipigs.

@entity3517 :: ('MESH:C564098', 'Disease') :: ['SMS', 'shear-modifying stent'] @entity756 :: ('255738', 'Gene') :: ['PCSK9'] @entity39751 :: ('p|SUB|D|374|Y', 'ProteinMutation') :: ['D374Y'] @entity1442 :: ('MESH:D020178', 'Disease') :: ['Advanced plaques'] @entity1856 :: ('MESH:D058226', 'Disease') :: ['fibroatheroma'] @entity453 :: ('MESH:D003324', 'Disease') :: ['coronary atherosclerotic plaques'] @entity850 :: ('MESH:D003251', 'Disease') :: ['stenosis']
@entity39751 :: (p|SUB|D|374|Y,ProteinMutation) :: ['D374Y']
