15289-s-bos

4 67 | Rebuttal AoVC in FH osteogenesis. The effect of fluid flow in the heart is responsible for the variable phenotype expression, depending on the radius of the specific anatomic location in the heart (i.e., artery vs. valve). Fluid hemodynamics in the heart depends on multiple factors, as derived by the Bernoulli equation for fluid flow (7). Bernoulli described flow through a column as being directly proportional to the change in pressure across the column and indirectly proportional to the resistance. The formula for flow through the heart is similar to Ohm’s law for electricity, as shown in Equation 1. Equation 1Q=ΔPR The entire formula for resistance for steady-state flow through a circular tube is shown in Equation 2, where η = viscosity and r = radius of the tube. Equation 2R=8ηLπr4 Equations 1 and 2 can be combined to provide the flow rate through a circular tube in terms of a pressure drop, which is described as Poiseuille’s law: Equation 3Q=πr48ηLΔP The differences in the rate of fluid flow depend on the radius of the anatomic structure, which is inversely proportional to the resistance. In addition, it is important to note the inverse r4dependence of the resistance to fluidflow. If the radius of the tube is halved, the pressure drop for a given flow rate and viscosity is increased by a factor of 16, because the flow rate is then proportional to the fourth power of the radius. The LDL-Density-Radius Theory (4) and the LDL-Density-Pressure Theory (5) provide the molecular hypothesis of the role of lipids in the differentiation of valve myofibroblasts into osteoblast-like cells responsible for the calcifying phenotype. Expression of the calcification in the coronary artery (8) occurs at a faster rate than the aortic valve secondary to the effect of the radius in these 2 anatomic locations in the heart. The present study (3) measured the level of calcification, and the results correlate the LDL concentration, LDL receptor gene expression, andfinally aMendelian randomization analysis to suggest a causal role of LDL-C in beginning aortic valve pathology. The first case report to demonstrate by histology the presence of atherosclerosis in the aortic