Background
Among the leading causes of mortality worldwide --- cardiovascular disease, diabetes, stroke, cancer, and a variety of other diseases --- many are, at least in part, caused by the body’s own inflammatory response. Ischemic heart disease, for example, is the leading cause of death in the United States.  Ischemic disease has been associated with elevated markers of inflammation, and certain pro-inflammatory molecules are proposed to play a role in development of the disease state.  

UCF researchers have identified a novel transcription factor called MCPIP (MCP-1-Induced protein), which was initially isolated from human monocytes after stimulation with MCP-1 (Monocyte chemoattractant protein-1).  MCPIP is expressed in monocytes, vascular endothelial cells, and cardiac myocytes and up-regulates members of the apoptotic gene family involved in the induction of cell death. MCP-1 induces cell death in cardiomyoblast cell line H9C2 via activation of MCPIP. Where MCPIP is associated with the disease state, inhibition of MCPIP activity, DNA binding, nuclear localization, etc., may be a therapeutic option for preventing or treating the disease.

Invention
A novel protein, designated MCPIP (MCP-Induced protein), has been shown to be elevated in human heart tissue with ischemic heart disease.

Application
A possible drug target for therapeutic intervention in heart disease. This target could be used to develop new drugs to prevent or treat ischemic heart disease, the number one killer in humans.

Advantages
•    MCPIP has been shown to be involved in development of ischemic heart disease in animal models and human cardiac tissue.
•    Because MCPIP induces expression of a variety of genes in response to MCP-1, MCPIP activation, over-expression, gene transfer, protein delivery, inhibition of activation, gene-knockout, inhibition by siRNA, and inhibition of nuclear localization, could represent therapeutic opportunities for the treatment of various cardiovascular diseases.  

Lead Inventor
PE Kolattukudy, Ph.D.  

Selected References
Liang J, Wang J, Azfer A, Song W, Tromp G, et al. A novel CCCH-zinc finger protein family regulates proinflammatory activation of macrophages. J Biol Chem 2008; 283(10): 6337–46.

Niu J, Azfer A, Zhelyabovska O, Fatma S, Kolattukudy PE. Monocyte chemotactic protein-1 promotes angiogenesis via a novel transcription factor MCPIP. J Biol Chem 2008; 283(21): 14542-51

Zhou L, Azfer A, Niu J, Graham S, Choudhury M, et al. Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ Res 2006; 98: 1–10.

Contact
Attn: Svetlana Shtrom, Ph.D., MBA
University of Central Florida
Office of Research and Commercialization
12201 Research Parkway, Suite 501
Orlando, Fl 32826-3246
Phone: 407.823.5150
Fax: 407.823.3299
sshtrom@mail.ucf.edu

UCF ID # 6962, 7647