Abstract P152: Downregulation Of Tissue-nonspecific Alkaline Phosphatase In Endothelial Cells Does Not Affect Calcification But Reduces Cardiac Function In Mice With Atherosclerosis

Abstract

Introduction: We have previously demonstrated that overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells increases vascular calcification and accelerates atherosclerosis. Whether TNAP activity in vascular endothelium is essential for intimal calcification and the progression of atherosclerosis is unknown. Hypothesis: We hypothesized that elimination of TNAP expression in endothelial cells would be sufficient to reduce intimal calcification associated with atherosclerosis. Methods: Endothelial TNAP knockout (KO) mice were developed on the background of the low density lipoprotein receptor mutation. Endothelial TNAP KO (n = 8) and control (n = 9) mice were fed a Western diet starting from 8 weeks and until 52 weeks of age. Cardiac structure and function were assessed by echocardiography. Calcium volume was measured in the aortic root and aortic arch area by microcomputed tomography (microCT). Data were analyzed using a 2-way ANOVA to calculate the effects of the genotype adjusted for sex. Results: MicroCT data did not show any statistically significant decrease in calcification in endothelial TNAP KO mice compared to controls; however, other cardiac parameters were affected by genotype. The physiological examination of the mice demonstrated that ablation of TNAP expression in the endothelium resulted in significant reduction in ejection fraction, stroke volume, and cardiac output in the absence of cardiac hypertrophy. Conclusion: Contrary to our hypothesis, TNAP has no effect on natural progression of calcified atherosclerosis; however, our data indicate that TNAP is required for protection of cardiac function under conditions of atherosclerosis in mice