COMPOSITIONS AND METHODS TO ENHANCE REVERSE CHOLESTEROL TRANSPORT
The present invention shows that pharmacological up regulation of SRB-1, ABC-A1 and LCAT genes collectively can be used to promote reverse cholesterol transport and increase circulating HDL cholesterol as treatment for atherosclerosis and related cardiovascular disorders.
1 . A method of promoting reverse cholesterol transport in a subject, the method comprising administration of an effective amount of an agent that up regulates reverse cholesterol transporter genes.
2 . A method of claim 1 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
3 . A method of claim 1 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
4 . A method of claim 1 when the agent is a synthetic organic molecule.
5 . A method of claim 1 when the synthetic organic molecule has a molecular weight of <700.
6 . A method of claim 1 wherein the subject is a SR-B1, ABC-A1 expressing mammal.
7 . A method of claim 6 , wherein mammal is a human.
8 . A method of increasing HDL in a subject, the method comprising administration of an effective amount of an agent that up regulates reverse cholesterol transporter genes.
9 . A method of claim 8 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
10 . A method of claim 8 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
11 . A method of claim 8 when the agent is a synthetic organic molecule.
12 . A method of claim 8 when the synthetic organic molecule has a molecular weight of <700.
13 . A method of claim 8 wherein subject is a SR-B1, ABC-A1 expressing mammal.
14 . A method of claim 13 , wherein mammal is a human.
15 . A method of treating dyslipidemia in a subject, the method comprising administration of an effective amount of an agent that up regulates reverse cholesterol transporter genes.
16 . A method of claim 15 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1 genes.
17 . A method of claim 15 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT genes.
18 . A method of claim 15 when the agent is a synthetic organic molecule.
19 . A method of claim 15 when the synthetic organic molecule has a molecular weight of <700.
20 . A method of claim 15 wherein subject is a SR-B1, ABC-A1 expressing mammal.
21 . A method of claim 20 , wherein mammal is a human.
22 . A method of treating cardiovascular disease in a subject, the method comprising administration of an effective amount of an agent that up regulates reverse cholesterol transporter genes.
23 . A method of claim 22 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
24 . A method of claim 23 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
25 . A method of claim 23 when the agent is a synthetic organic molecule.
26 . A method of claim 23 when the synthetic organic molecule has a molecular weight of <700.
27 . A method of claim 23 wherein subject is a SR-B1, ABC-A1 expressing mammal.
28 . A method of claim 27 , wherein mammal is a human.
29 . A method of claim 22 , wherein cardiovascular disease is atherosclerosis.
30 . A method of up regulating SR-B1 and ABC-A1 in a cell, the method comprising contacting the cell with an effective amount of an agent that up regulates reverse cholesterol transporter genes.
31 . A method of claim 30 , wherein the cell is a macrophage or a liver cell.
32 . A method of identifying compounds that up regulate reverse cholesterol transporter genes in a cell.
33 . A method of claim 32 wherein the cell is a macrophage or a liver cell.
34 . A method of claim 32 wherein the compound is a synthetic organic molecule with molecular weight of <700.
35 . A method of claim 32 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
36 . A method of claim 32 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
37 . A method of identifying compounds that increase HDL in a subject by up regulating reverse cholesterol transporter genes.
38 . A method of claim 37 wherein compound is a synthetic organic molecule with molecular weight of <700.
39 . A method of claim 37 wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
40 . A method of claim 37 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
41 . A method of identifying compounds that treat atherosclerosis by up regulating reverse cholesterol transporter genes.
42 . A method of claim 41 wherein compound is a synthetic organic molecule with molecular weight of <700.
43 . A method of claim 41 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
44 . A method of claim 41 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT genes.
45 . A method of identifying compounds that treat cardiovascular disorders by up regulating reverse cholesterol transporter genes.
46 . A method of claim 45 , wherein compound is a synthetic organic molecule with molecular weight of <700.
47 . A method of claim 45 , wherein the up regulated reverse cholesterol transporter genes are SR-B1 and ABC-A1.
48 . A method of claim 45 , wherein the up regulated reverse cholesterol transporter genes are SR-B1, ABC-A1, and LCAT.
49 . A method of treating atherosclerosis in a subject, the method comprising administrating an effective amount of compound of claim 41 with a CETP-inhibitor.
50 . A method of increasing HDL in a subject, the method comprising administrating an effective amount of compound of claim 37 with a CETP-inhibitor.