Coupling Hemodynamics and Protein Regulation In Cerebral Saccular Aneurysms

Marjan Rafat1, Martin Heller2, Howard A. Stone1, and Debra T. Auguste1. (1) School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, (2) Micro- and Nanotechnology, Technical University of Denmark, Building 345 East, DK-2800, Kongens Lyngby, Denmark

The mechanisms behind aneurysm growth and rupture are unknown. Additional analysis of the relationship between hemodynamics, mechanical forces, and biological response may enable aneurysm prediction, improve diagnosis, and allow development of new treatment approaches. We examined the hemodynamic profiles of clinically relevant aneurysm geometries for a range of physiological Reynolds numbers (100 < Re < 400) by numerically solving the Navier-Stokes equation. We identified flow regimes where shear stress and mass transfer limitations occur and created an in vitro model that mimics aneurysms using a poly(dimethylsiloxane) (PDMS) mold attached to glass. In order to analyze the cellular response to shear stress and flow profiles, we seeded human aortic endothelial cells (HAEC) onto these constructs and flowed through media at various flow rates (100, 200, and 400 mL/min) and viscosities (3, 4, and 5 cP) that are comparable to physiological conditions. We evaluated the regulation of surface receptors (PECAM-1, ICAM-1, and E-Selectin) as well as extracellular matrix remodeling components (matrix metalloproteinase-2 and 9, collagen types I and IV, elastin, and laminin). Understanding protein regulation in response to physical flows could implicate new strategies for vascular tissue engineering and drug delivery.