FA 5 Progress Report WV-INBRE - Joan C. Edwards School of ...

Program Director/Principal Investigator (Last, First, Middle): Rankin, Gary O 50MECHANISM OF ACTION OF STATINS ON ENDOTHELIAL CELL FUNCTION (0025)TYPE: Research Subproject%IDeA $: 5.000% IDeA $: 175,625INVESTIGATOR, DEGREEKreisberg, Robert PHDPrimerano, Donald A PHDDEPARTMENTBiologyBiochemistry &MicrobiologyNON-HOST INSTITUTION: STATE,COUNTRYWest Liberty University, Wv UsaTotal # human subjects expected for entire study: 0Total # human subjects enrolled to date: 0SUBPROJECT DESCRIPTIONIschemic heart disease is the generic designation for a group of closely related syndromes resulting frommyocardial ischemia – an imbalance between the supply and demand for oxygenated blood. Until recently,the pathogenesis was attributed to reduction in coronary blood flow due to atherosclerotic coronary arteryobstruction. The process is actually much more complicated. Recent data suggest the pathogenesis ofatherosclerosis includes endothelial response to injury and compares to chronic inflammation of the vascularwall. Lipid-laden macrophages recruited to the vascular wall due to endothelial activation may play a role inthe stability of the atherosclerotic plaque; rupture of the plaque due to release of matrix metalloproteinasesfrom the macrophages causes exposure of the subintimal space resulting in thrombus formation andobstruction (1). Recently, experimental evidence suggests that 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGA-CoA) inhibitors, such as the statins used to treat hypercholesterolemia, alsoattenuate inflammation of the vascular wall independently of their lipid-lowering effects (2). The long-rangegoal of the proposed research is to uncover the molecular mechanisms of endothelial cell and macrophageactivation by minimally-modified LDL (MM-LDL) and to determine whether statins inhibit this activation. Theoverall objective of this project is to identify the signaling processes affected by statin treatment.SUBPROJECT PROGRESS• Multiple abstract publications.• Over 25 undergraduate students involved in the Cardiovascular Research Project.o Greater than 90% matriculated into post-graduate education (Medical , Graduate, Dental,Pharmacy, and Physician Assistant Programs)• Received over $600,000 in competitive WVEPSCoR funding to have a Summer UndergraduateResearch Program (2005-2010) At West Liberty University. Over 90 students participated in thisprogram.• Fifteen different students presented their research results at both state and nationwide scientificconferences.• The laboratory received a grant (Rosuvastatin) from AstraZeneca to look at compareRosuvastatin to Lovastatin in its ability to inhibit IL8 production by Human Aortic Endothelial Cells.o We have some very interesting results but unfortunately, I am unable to disclose at this timedue to the confidentiality statement I signed.• With the success of the Rosuvastatin experiments we are currently in serious discussions withAstraZeneca to use our current laboratory techniques to look at one of their new platelet drugs.• Currently repeating some IL6 experiments (cleaning up data) so that a manuscript can besubmitted for publicationPROTECTION AGAINST RESEARCH RISKSN 1. Will human subjects be involved next year?N 2. Will vertebrate animals be used next year?N 3. Will recombinant DNA experiment(s) be conducted next year?Y 4. Are there potential hazards to laboratory workers (carcinogens, pathogens, ionizing radiation, etc.)involved in the proposed research for next year? If yes, identify:PHS 2590 (Rev. 06/09)Continuation Format Page