Methods and compositions to lower plasma cholesterol levels

1. A method to determine if a compound causes a change in the structure of apolipoprotein B-100 in a cholesterol-containing low density lipoprotein thus increasing the binding of an epitope on the apolipoprotein B-100 to the LDL-receptor, comprising:

(i) mixing the compound with and allowing it to bind to cholesterol-containing low density lipoprotein forming a complex;

(ii) exposing the complex to a first capture antibody that is attached to a solid phase material and is directed to the epitope on apolipoprotein B-100 that binds to the LDL-receptor, forming a combination;

(iii) adding a second antibody which binds to the combination;

(iv) detecting the second antibody bound to the combination by the addition of a third antibody that binds the second antibody and to which is attached a label;

(v) quantifying the amount of the captured complex by quantifying the amount of label; and

(vi) comparing the amount of cholesterol-containing low density lipoprotein captured by the assay to a control, wherein an increase in the amount of cholesterol-containing low density lipoprotein captured indicates a change in the structure of apoB-100 in the cholesterol-containing low density lipoprotein, thus increasing binding to the low density lipoprotein receptor.

2. The method of claim 1 , wherein the control is low density lipoprotein in the absence of test compound.

3. A method for assessing whether a compound first binds to a cholesterol-containing lipoprotein, enhancing the binding of the cholesterol-containing lipoprotein to a low density lipoprotein hepatic receptor and thus lowering plasma cholesterol, the method comprising:

(a) allowing the compound to form a complex with a cholesterol-containing lipoprotein in vivo,

(b) isolating the resulting complex, and

(c) determining whether the formation of the complex causes a change in the three dimensional conformation of apoB-100 in the cholesterol-containing lipoprotein that enhances the binding of the lipoprotein to the LDL hepatic receptor.

4. The method of claim 3 , wherein the formation of the complex is determined by a sandwich immunoreactivity assay.

5. The method of claim 3 , wherein the formation of the complex is determined using agarose electrophoresis.

6. The method of claim 3 , wherein the cholesterol-containing low-density lipoprotein is LDL.

7. The method of claim 3 , wherein the cholesterol-containing low-density lipoprotein is VLDL.

8. A method to determine if a compound causes a change in the structure of apolipoprotein B-100 in a cholesterol-containing low density lipoprotein thus increasing the binding of an epitope on the apolipoprotein B-100 to an LDL-receptor, comprising:

(i) mixing the compound with and allowing it to bind to cholesterol-containing low density lipoprotein forming a complex;

(ii) exposing the complex to a first capture antibody that is attached to a solid phase material and is directed to the epitope on apolipoprotein B-100 that binds to the LDL-receptor, forming a combination;

(iii) adding to the combination a second antibody which binds the apoB-100 in the combination and to which is attached a label;

(iv) quantifying the amount of the captured complex by quantifying the amount of label; and

(v) comparing the amount of cholesterol-containing low density lipoprotein quantified in step (iv) to a control, wherein an increase in the amount of cholesterol-containing low density lipoprotein captured indicates a change in the structure of apoB-100 in the cholesterol-containing low density lipoprotein, thus increasing binding to the low density lipoprotein receptor.

9. The method of claim 8 , wherein the control is low density lipoprotein in the absence of test compound.