Animal Models of Vascular Injury Dr. Elazer Edelman’s work is directed towards understanding atherosclerotic arterial disease. Both the means by which atherosclerosis is kept in check and the mechanisms that lead to the decompensation that results in unstable coronary syndromes is of significant interest to Dr. Edelman. Using animal models of vascular injury that permit examination of isolated lesions and specific pharmacologic manipulation of individual lesions, Dr. Edelman’s most recent focus has been on the understanding of the blood vessel’s endothelial monolayer and the examination of basic physiology of vascular drug delivery.
Endothelial Monolayer: Studies are underway to understand the endothelial cell (EC) as a bioregulator. Dr. Edelman has determined that local environment and substratum- EC interactions determine EC immune identity and local immune regulation. Therefore, he concludes that the health of the EC is defined not only in terms of density but also by immune modulation.
Vascular Drug Delivery: Dr. Edelman’s studies have determined that the distribution patterns of eluting drugs are found to be dependent on ultrastructural aspects of target vessels, flow over and through vessels, systemic and environmental states, as well as physico-chemical properties of individual drugs. Determination of the impact of arterial composition, geometry and ultrastructure on drug distribution and drug effect is now being studied.
Models of arterial injury and local drug delivery are examined in both the study of the endothelial monolayer and the basic physiology of vascular drug delivery: Studies are monitored using a variety classic and modern techniques in molecular, cell and tissue biology as well as immunocytochemistry to define the nature of cellular response, selective dyes to demonstrate changes in vascular permeability, strength of materials testing to detest changes in elastic properties, and digital signal processing of video images of injected injured arteries to define the different microvascular structures surrounding diseased blood vessels.
References:
Schubert SY, Benarroch A, Ostvang J, Edelman ER. Regulation of endothelial cell proliferation by primary monocytes. Arterioscler Thromb Vasc Biol 2008 Jan; 28(1)97-104.
Methe H, Hess S, Edelman ER. Endothelial Immunogenicity, A Matter of Matrix Microarchitecture. Thromb Haemost 2007 Aug; 98(2):278-282.
Morss AS, Edelman ER. Glucose modulates basement membrane fibroblast growth factor-2 via alterations in endothelial cell permeability. J Biol Chem. 2007 May; 282(19):14635-44.
Balakrishnan B, Dooley J, Kopia G, Edelman ER. Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. J Control Release 2007 Nov; 123(2):100-08.
Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: Molecular, cellular and vascular behavior. J Am Coll Cardiol 2007 Jun; 49(25):2379-93.
Methe H, Balcells M, Alegret MD, Santacana M, Molins B, Hamik A, Jain M, Edelman ER. Vascular Bed Origin Dictates Flow Pattern Regulation of Endothelial Adhesion Molecule Expression. Am J Physiol Heart Circ Physiol 2007 May; 292(5):H2167-75.
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