Biomechanical and Microstructural Properties of Common Carotid Arteries from Fibulin-5 Null Mice

Abstract

Alteration in the mechanical properties of arteries occurs with aging and disease, and arterial stiffening is a key risk factor for subsequent cardiovascular events. Arterial stiffening is associated with the loss of functional elastic fibers and increased collagen content in the wall of large arteries. Arterial mechanical properties are controlled largely by the turnover and reorganization of key structural proteins and cells, a process termed growth and remodeling. Fibulin-5 (fbln5) is a microfibrillar protein that binds tropoelastin, interacts with integrins, and localizes to elastin fibers; tropoelastin and microfibrillar proteins constitute functional elastic fibers. We performed biaxial mechanical testing and confocal imaging of common carotid arteries (CCAs) from fibulin-5 null mice (fbln5 ^−/−) and littermate controls (fbln5 ^+/+) to characterize the mechanical behavior and microstructural content of these arteries; mechanical testing data were fit to a four-fiber family constitutive model. We found that CCAs from fbln5 ^−/− mice exhibited lower in vivo axial stretch and lower in vivo stresses while maintaining a similar compliance over physiological pressures compared to littermate controls. Specifically, for fbln5 ^−/− the axial stretch λ = 1.41 ± 0.07, the circumferential stress σ _θ  = 101 ± 32 kPa, and the axial stress σ _z  = 74 ± 28 kPa; for fbln5 ^+/+ λ = 1.64 ± 0.03, σ _θ  = 194 ± 38 kPa, and σ _z  = 159 ± 29 kPa. Structurally, CCAs from fbln5 ^−/− mice lack distinct functional elastic fibers defined by the lamellar structure of alternating layers of smooth muscle cells and elastin sheets. These data suggest that structural differences in fbln5 ^−/− arteries correlate with significant differences in mechanical properties. Despite these significant differences fbln5 ^−/− CCAs exhibited nearly normal levels of cyclic strain over the cardiac cycle.