Does Tissue-Nonspecific Alkaline Phosphatase Deficiency in Hepatocytes Affect Cardiac Function and Arterial Stiffness in Mice with Atherosclerosis?

Student Presenter(s): Harshul Singh, Saud A. Nasruddin, Neil Kaungumpillil, Danyang Ma, and Michael Gao
Faculty Mentor: Olga Savinova
School/College: Osteopathic Medicine, Old Westbury

Vascular calcification, mineral deposits in the blood vessels and valves, could lead to arterial stiffness, stenosis of the valves and heart failure. Tissue-nonspecific alkaline phosphatase (TNAP) impacts cardiovascular mortality by increasing atherosclerotic plaque calcification. Higher circulating TNAP levels are associated with increased cardiovascular risk. Inhibiting TNAP could improve therapeutic approaches by understanding the effect of calcification on atherosclerosis. Our study was designed to evaluate whether a genetic deficiency of TNAP in hepatocytes can improve cardiovascular outcomes in a mouse model of atherosclerosis. 9-13 mice of each sex were included in the study. All mice had a mutation in the low-density lipoprotein receptor and were exposed to an atherogenic western diet starting from 8 weeks of age for 15 weeks (an intermediate time-point) or for up to one year of age. The echocardiographic data were collected, and the results of the intermediate time-point were analyzed. Data were compared by a two-way ANOVA accounting for sex (males vs. females) and genotype (hepatocyte TNAP knockout vs. wild-type TNAP). No significant effects of TNAP deficiency were observed at the intermediate time-point of the study, we found no significant differences between groups with respect to the left ventricular structure and function and the aortic stiffness. A long-term effect of TNAP deficiency on atherosclerotic calcification awaits further testing.