Atherogenics, Inc.

Jayraz Luchoomun

James A Sikorski

Uday Saxena

Charles Q Meng

Charles A Kunsch

Signe Erickson Varner

Xilin Chen

This invention is in the area of regulatory DNA sequences and their methods of use. Specifically, DNA sequences found in the regulatory region of cytoprotective genes are described that are termed cytoprotective response elements. DNA constructs also are provided that include cytoprotective response elements operably linked to heterologous protein coding sequence, as well as cells and non-human organisms that include the cytoprotective response elements optionally operably linked to a heterologous protein coding sequence, and a method for screening for a compound that increases mRNA or protein regulated by a cytoprotective response element. It has been discovered that the cytoprotective response elements mediate the coordinate activation of certain genes that protect cells from damaging effects of oxidative stress, and that they do so, for example during conditions of hemodynamic shear stress.

Protection against oxidative stress and inflammation by a cytoprotective response element

It has been discovered that certain selected ethers of probucol, and their pharmaceutically acceptable salts or prodrugs, are useful for increasing circulating HDL cholesterol. These compounds may also improve HDL functionality by (a) increasing clearance of cholesteryl esters, (b) increasing HDL-particle affinity for hepatic cell surface receptors or (c) increasing the half life of apoAI-HDL.

Compounds and methods to increase plasma HDL cholesterol levels and improve HDL functionality

Growing community of inventors

Lilburn, GA, United States of America

Jayraz Luchoomun