Abstract
Introduction: Increased expression of TNAP (tissue-nonspecific alkaline phosphatase) in macrophages exacerbates atherosclerotic calcification in a mouse model. However, whether or not TNAP is necessary in the progression of calcification, or for proper cardiac function has yet been studied. Objective: The purpose of this study was to test the effect of TNAP ablation in macrophages on atherosclerotic plaque calcification and cardiovascular physiology, and compare it to a wild type situation. Methods: Macrophage-specific WHC-mTNAP knockout (KO) mice were produced in our colony by intercrossing floxed alpl transgenic mice ( alpl gene encodes TNAP) and macrophage-specific CRE recombinase mice, in which CRE was expressed under the control of the lysozyme gene promoter. The macrophage TNAP KO strain was developed on the background of homozygous WHC (“wicked high cholesterol”) mutation in the low density lipoprotein receptor gene. WHC-TNAP KO (n=10) and their WHC littermates (n=9) were placed on an atherosclerosis inducing diet at 8 weeks of age. The mice were maintained on the diet for 44 weeks, or until they turned 52 weeks. Microcomputed tomography (microCT) analyses of calcification in the aortic roots and arches were performed ex vivo . Echocardiographic studies were performed to assess cardiac structure and function at 52 weeks of age. Data were analyzed via a 2-way ANOVA to calculate the effect of TNAP ablation on calcification and cardiovascular physiology while adjusting for sex. Results: CT data showed no significant difference in calcification levels between the two genotypes. Cardiac parameters such as left ventricular (LV) mass, LV diameter and wall thickness, ejection fraction, fractional shortening and cardiac output also showed no signifgant difference between the two genotypes. Conclusion: Our data suggest that, despite TNAP expression in macrophages being sufficient to induce calcification of atherosclerotic plaques, it is not necessary in the calcification process. To the extent of our study, the ablation of TNAP in macrophages does not appear to have any consequences in a mouse model of atherosclerosis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Arteriosclerosis, Thrombosis, and Vascular Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
