The stiffness and structural integrity of the arterial wall depends primarily on the organization of the extracellular matrix and the cells that fashion and maintain this matrix. Fundamental to the latter is a delicate balance in the continuous production and removal of structural constituents and the mechanical state in which such turnover occurs. Perturbations in this balance due to genetic mutations, altered hemodynamics, or pathological processes result in diverse vascular phenotypes, many of which have yet to be well characterized biomechanically. In this paper, we emphasize the particular need to understand regional variations in the biaxial biomechanical properties of central arteries in health and disease and, in addition, the need for standardization in the associated biaxial testing and quantification. As an example of possible experimental methods, we summarize testing protocols that have evolved in our laboratory over the past 8 years. Moreover, we note advantages of a four fiber family stress – stretch relation for quantifying passive biaxial behaviors, the use of stored energy as a convenient scalar metric of the associated material stiffness, and the utility of appropriate linearizations of the nonlinear, anisotropic relations both for purposes of comparison across laboratories and to inform computational fluid-solid-interaction models. We conclude that, notwithstanding prior advances, there remain many opportunities to advance our understanding of arterial mechanics and mechanobiology, particularly via the diverse genetic, pharmacological, and surgical models that are, or soon will be, available in the mouse.

The embryonic lineage of intramural cells, microstructural organization of the extracellular matrix, local luminal and wall geometry, and haemodynamic loads vary along the length of the aorta. Yet, it remains unclear why certain diseases manifest differentially along the aorta. Toward this end, myriad animal models provide insight into diverse disease conditions-including fibrosis, aneurysm and dissection-but inherent differences across models impede general interpretations. We examined region-specific cellular, matrix, and biomechanical changes in a single experimental model of hypertension and atherosclerosis, which commonly coexist. Our findings suggest that (i) intramural cells within the ascending aorta are unable to maintain the intrinsic material stiffness of the wall, which ultimately drives aneurysmal dilatation, (ii) a mechanical stress-initiated, inflammation-driven remodelling within the descending aorta results in excessive fibrosis, and (iii) a transient loss of adventitial collagen within the suprarenal aorta contributes to dissection propensity. Smooth muscle contractility helps to control wall stress in the infrarenal aorta, which maintains mechanical properties near homeostatic levels despite elevated blood pressure. This early mechanoadaptation of the infrarenal aorta does not preclude subsequent acceleration of neointimal formation, however. Because region-specific conditions may be interdependent, as, for example, diffuse central arterial stiffening can increase cyclic haemodynamic loads on an aneurysm that is developing proximally, there is a clear need for more systematic assessments of aortic disease progression, not simply a singular focus on a particular region or condition.

The primary function of central arteries is to store elastic energy during systole and to use it to sustain blood flow during diastole. Arterial stiffening compromises this normal mechanical function and adversely affects end organs such as the brain, heart, and kidneys. Using an angiotensin-II infusion model of hypertension in wild-type mice, we show that the thoracic aorta exhibits a dramatic loss of energy storage within two weeks that persists for at least four weeks. This diminished mechanical functionality results from increased structural stiffening due to an excessive accumulation of adventitial collagen, not a change in the intrinsic stiffness of the wall. A detailed analysis of the transmural biaxial wall stress suggests that the exuberant production of collagen results more from an inflammatory response than a mechano-adaptation, hence reinforcing the need to control inflammation, not just blood pressure. Although most clinical assessments of arterial stiffening focus on intimal-medial thickening, these results suggest a need to measure and control the highly active and important adventitia.

Central artery stiffness has emerged over the past 15 years as a clinically significant indicator of cardiovascular function and initiator of disease. Loss of elastic fiber integrity is one of the primary contributors to increased arterial stiffening in aging, hypertension, and related conditions. Elastic fibers consist of an elastin core and multiple glycoproteins; hence defects in any of these constituents can adversely affect arterial wall mechanics. In this paper, we focus on mechanical consequences of the loss of fibulin-5, an elastin-associated glycoprotein involved in elastogenesis. Specifically, we compared the biaxial mechanical properties of five central arteries-the ascending thoracic aorta, descending thoracic aorta, suprarenal abdominal aorta, infrarenal abdominal aorta, and common carotid artery-from male and female wild-type and fibulin-5 deficient mice. Results revealed that, independent of sex, all five regions in the fibulin-5 deficient mice manifested a marked increase in structural stiffness but also a marked decrease in elastic energy storage and typically an increase in energy dissipation, with all differences being most dramatic in the ascending and abdominal aortas. Given that the primary function of large arteries is to store elastic energy during systole and to use this energy during diastole to work on the blood, fibulin-5 deficiency results in a widespread diminishment of central artery function that can have significant effects on hemodynamics and cardiac function.