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 @entity39751 - XXXX 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']
@entity756 :: (255738,Gene) :: ['PCSK9']
