Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

AbstractObjective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery

The role of hemodynamics in the development of the outflow tract of the heart

The question whether, and if so to what extent, hemodynamic forces and mechanical stimuli do modulate the morphogenesis of the vascular system is a century-old problem. It is important especially in the outflow tract where a spiraling septum develops in and after a strong bend in the tube. Spiraling patterns of the flow in bends are well known. Of the mechanical stimuli that can potentially exert an effect on morphogenesis, wall shear stress is the most likely candidate; a number of genes that are expressed in the cardiovascular system have shear-stress responsive elements in their regulatory units. Recent investigations have clearly shown that the disturbance of normal hemodynamic conditions results in maldevelopment of the heart. However, an experimental model alone is necessary, but not sufficient to identify the intermediate steps of the interaction between blood flow and tissue remodeling in the developing cardiovascular system, certainly at Reynolds numbers and Dean numbers that are very small. Therefore, a model with a simple geometry has been created, using the ComFlo software: a fully 3D computational fluid-dynamics code that solves the Navier-Stokes equations on a Cartesian grid. A first assessment of the possible influence of a strong curvature, with biological realistic dimensions, was made using steady-flow conditions. Since both the Reynolds number and the Womersley number (indicating the influence of the pulsatility on the velocity profile of the flow) are extremely low, it is likely that these flow patterns do not differ significantly from those under pulsatile conditions. A first assessment of the effects of the strong curvature on the flow under the given circumstances showed only very small secondary velocities and negligible heterogeneity of the wall shear stress, even in the presence of a strong secondary flow pattern in the inlet of the tube.