Composition and method for treatment and prevention of restenosis

A composition for treating a cell proliferation disorder comprising:

• an inhibitor of smooth muscle cell proliferation comprising at least one isolated protein or polypeptide chosen from the group consisting of:
• PARIS-1, PARIS-2 and PARIS-3,
• biologically active portions of PARIS-1, PARIS-2, PARIS-3 or PARIS-4, wherein biological activity comprises inhibition of smooth muscle cell proliferation, and
• polypeptides having at least 24% amino acid identity to SEQ. ID NO:1, SEQ. ID NO:2, SEQ. ID NO:3 or SEQ ID NO:4;
• and
• optionally, a carrier.

A method for identifying an inhibitor of smooth muscle cell proliferation comprising:

• extracting RNAs from growing vascular smooth muscle cells from a first animal model that is restenosis-resistant with respect to balloon injury to a blood vessel in said first animal model, to provide a first pool of isolated RNAs;
• generating a first cDNA pool from said first pool of RNAs;
• extracting RNAs from growing vascular smooth muscle cells from a second animal model that is restenosis-prone with respect to balloon injury of a blood vessel in said second animal model, to provide a second pool of isolated RNAs;
• generating a second cDNA pool from said second pool of isolated RNAs;
• identifying cDNAs that are present in said first cDNA pool in a greater amount than in said second cDNA pool, to provide a pool of upregulated cDNAs;
• identifying a first set of genes that correspond to said upregulated cDNAs;
• out of said first set of genes, identifying a subset of genes that encode soluble proteins which are secreted to a greater extent by vascular smooth muscle cells from said first animal model than from said second animal model, to provide a group of upregulated genes encoding soluble proteins;
• confirming that at least one said encoded soluble protein is expressed to a greater extent in vascular smooth muscle cells from said first animal model than in vascular smooth muscle cells from said second animal model, to identify at least one upregulated soluble protein inhibitor of smooth muscle cell proliferation;
• optionally, expressing at least one gene coding for said upregulated soluble protein;
• optionally, purifying said at least one upregulated soluble protein, to provide a purified upregulated soluble protein;
• and
• optionally, adding said purified protein to vascular smooth muscle cells in cell culture medium and confirming that said protein is active for retarding proliferation of said vascular smooth muscle cells.