Cherepanova, Olga A
Primary Appointment
Molecular Physiology and Biological Physics
Contact Information
Email: oac4x@virginia.edu
Research Interests
Molecular mechanisms responsible for the phenotypic transition of vascular cells, including smooth muscle cells (SMCs), endothelial cells (ECs) and macrophages during atherogenesis and vascular injury
Research Description
Project 1. Role of the embryonic stem cell pluripotency factor OCT4 in the regulation of phenotypic transition of vascular cells after vascular injury, under the contexts of hyperlipidemia and cancer.
Recently, we found that the embryonic stem cell factor OCT4 plays an athero-protective role in SMCs by regulating SMC phenotypic transition, including migration and SMC investment into fibrous cap {Cherepanova et al., Nature Med, 2016}.
The overall goal of current project is to test if activation of the pluripotency factor OCT4 within ECs plays a key functional role during atherosclerosis development through regulation of EC activation and dysfunction.
Project 2. Development of an anti-oxidized phospholipid neutralizing antibody as an atheroprotective therapeutic agent.
Oxidized phospholipids (OxPL), such as oxidized PAPC (1-palmitoil-2-arachodonoyl-sn-glycero-3-phosphorylcholine) and its derivatives have been shown to be the principal biologically active components of minimally oxidized LDL, whose role in cardiovascular diseases is well recognized including activation of inflammatory processes within the major cell types in the disease including ECs, SMCs and macrophages. We have recently generated an anti-oxidized phospholipid (oxPL) autoantibody (10C12) that demonstrates potent OxPL neutralizing activity in vitro, as well as the ability to inhibit macrophage accumulation within arteries of atherosclerotic ApoE KO mice fed a high fat diet for 4 weeks. The overall goal of current project is to test whether this 10C12 anti-OxPL antibody can decrease and/or reverse development of atherosclerosis in late stages of the disease since this would mimic likely clinical paradigms.