Abstract 17183: Genetically Engineered Calcification Increases Surface Roughness and Changes the Distribution of Atherosclerotic Plaques in Mice With Atherosclerosis

Background: Atherosclerosis is an inflammatory disease that contributes significantly to cardiovascular mortality. Arterial stiffening due to calcification can coexist with or directly influence pathogenesis of atherosclerosis. We hypothesize that arteriosclerosis caused by genetically engineered calcification in mice redistributes shear stress on the endothelial cells, which in turn leads to further accelerated rate of plaque formation. Methods: All of the mice had an LDL receptor mutation and were fed pro-atherogenic diet (1.25% cholesterol). The case group overexpressed tissue-nonspecific alkaline phosphatase in endothelial cells (eTNAP). The luminal surfaces of descending thoracic aorta (TA) and suprarenal abdominal aorta (AA) were scanned using Sensofar S Neox optical confocal microscope at 1 μm vertical resolution. The surface topographies per sample, each measuring 500 x 700 microns, were analyzed for ISO 25178-2 areal roughness parameters using SensoMap. Parameters were compared by t test (n=5 eTNAP, n=6-7 control). Results: We observed a significant difference in the incidence as well as the morphology of the plaques in the eTNAP group compared to control mice. There was a 4.8 fold increase in the number of topological motifs in the thoracic aorta of the eTNAP vs. controls (p < 0.01). Similarly, the number of motifs was increase in the abdominal aorta of the eTNAP mice compared to controls (2.8 fold; p=0.06). The average area of the motifs was significantly larger in the controls compared to the eTNAP group in both segments of the aorta (p=0.06 TA; p < 0.05 AA). The maximum height of the lesions in the TA was not different between the groups (p=0.62), however increased by 74% in the abdominal aorta of the eTNAP compared to controls (p Conclusion: Arteriosclerosis increases surface roughness. In our model, the abdominal region had a high incidence of taller, irregular lesions whereas those in the thoracic aorta were flatter and more spaced. The high resolution scans will be further used to study the hemodynamic disturbances to the endothelial cells using flow dynamics simulations.