Queen's University at Kingston

The University of Chicago

Shui-Pang Tam

Robert Kisilevsky

Zongchao Jia

John B Ancsin

Xia Zhang

Peptides and mimetics of selected domains of mammalian serum amyloid A isoform 2.1 (SAA2.1) and compounds and compositions thereof are provided that enhance the effect on macrophage cholesterol ester hydrolase activity and/or inhibit acyl CoA:cholesterol acyl transferase activity. Methods of using these compositions in the treatment and/or prevention of atherosclerosis as well as coronary heart disease and cardiovascular disease are also provided.

Compositions and methods for treating atherosclerosis

The present invention relates, in general, to antioxidant responsive elements (AREs). In particular, the present invention relates to a DNA construct comprising an ARE having the DNA sequence 5'-RGR AC NNN GCT-3' (SEQ ID NO: 1) operably linked to a heterologous protein coding sequence; cells and non-human organisms comprising the DNA construct; a method of screening for a compound that increases transcription of an MRNA regulated by an antioxidant responsive element; and a purified compound that binds to an antioxidant responsive element.

Antioxidant responsive element

Methods for screening for a drug that increases expression of the human apolioprotein (apo) AI gene and related DNA constructs. A first method has the steps of: (a) introducing into mammalian cells a DNA construct including, functionally joined together in the 5'.fwdarw.3' direction of transcription, (i) at least one copy of a drug-responsive element (DRE) having at least about 80% homology with the DNA sequence 5'-G/C N T/G A/G GCTGGG-3', (ii) a heterologous promoter, (iii) a reporter gene and (iv) an untranslated region including a functional polyadenylation signal; (b) growing a first culture of the cells in the absence of drug; (c) lysing the first culture to produce a first extract; (d) assaying the first extract for activity of a protein encoded by the reporter gene; (e) growing a second culture of the cells in the presence of the drug; (f) lysing the second culture to produce a second extract; (g) assaying the second extract for activity of the protein encoded by the reporter gene; and (h) comparing the activities of the first extract and the second extract. A second method uses a different DNA construct including (i) a promoter region of the human apo AI gene including at least one copy of a drug-responsive element (DRE) having at least about 80% homology with the DNA sequence 5'-G/C N T/G A/G GCTGGG-3', (ii) a reporter gene and (iii) an untranslated region including a functional polyadenylation signal. A third method involves stably maintaining the introduced DNA in the cells.

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Kingston, Canada

Shui-Pang Tam