Experimental hypercholesterolemia in genetic ApoE -/- /Lrp5 -/- mice: Proof of principle

Abstract

The low-density lipoprotein-related receptor 5 and 6 (Lrp5 and Lrp6) genes were cloned in 1998 based on their homology with the low-density lipoprotein receptor (LDLR) [1-4]. Mutations in either LRP5 or LRP6, proteins have caused a number of disease processed in the field of bone [5, 6], and have been associated with cardiovascular disease [4, 7-9]. The LDL-Density-Pressure theory [10] combines the structure, function analysis of these co-receptors with the results from the genetic studies to provide a unique hypothesis for the role of these receptors in the heart. This chapter provides the genetic mouse evidence to demonstrate that in the presence of experimental hypercholesterolemia, Lrp5/6 receptors, Runx2 genes are up-regulated in the presence of cholesterol and mediate calcification by MicroCT analysis.