Poster Topical Area: Aging and Chronic Disease
Poster Board Number: 79
Anti-atherogenic Effects of T0901317-loaded Nanoparticles in LDL Receptor Knockout Mice
Jie Liu, Jia Zhang, Yujiao Zu, Chuan Li, Jun Cao, Rownock Afruza, Lei Hao, Shu Wang*
Department of Nutritional Sciences, Texas Tech University, Lubbock, TX 79409 USA.
Key words: Atherosclerosis, nanoparticle, T0901317, fatty liver
Objectives: T0901317 (T) can dramatically regress atherosclerosis by activating macrophage liver X receptors in atherosclerosis animal models including LDL receptorknockout (LDLr-/-) mice. However, T's low aqueous solubility and lipogenic side effects hinder its application in atherosclerosis treatment. We have successfully made T-loaded nanoparticles (Tnano) and ligand–coated Tnano (LTnano), which increase T's aqueous solubility. LTnano target THP-1 derived macrophages and primary mouse macrophages through binding to their cluster of differentiation 36 receptors. The objectives of the study are to determine anti-atherosclerotic effects of Tnano and LTnano on preexisting atherosclerosis, and to measure their hepatic lipogenic adverse effects in LDLr-/- mice.
Methods: Twenty-five male LDLr-/- mice were fed an atherogenic diet for 22 weeks. During week 13-22, they were weekly intravenously injected with one of the followings: 1XPBS control, free T, Tnano, LTnano, void nanoparticles (Vnano), ligand-coated Vnano (LVnano). T dose was 196 μg/kg body weight/week. Body weight and body composition were measured weekly. After sacrifice, hearts, aortas and livers were collected. The aortas were opened longitudinally and imaged under a microscope. The en face analysis of atherosclerotic lesion areas was conducted using an NIH Image J software. Liver fat content was measured using an EchoMRI system. Liver sections were stained with hematoxylin and eosin.
Results: As compared to 1XPBS, LTnano, Tnano and free T decreased lesion areas by about 45%, but these three groups did not have significant differences. There were no significant differences in mouse body weight, body composition, liver lipid content and deposition among all treatment groups<./p>
Conclusions: Intravenous injection of free T, Tnano and LTnano at the studied dose decreased atherosclerotic lesion areas, and did not increase hepatic lipogenic adverse effects.
Texas Tech University