Investigation of Pathophysiological Aspects of Aortic Growth, Remodeling, and Failure Using a Discrete-Fiber Microstructural Model

Abstract

Aortic aneurysms are inherently unpredictable. One can never be sure whether any given aneurysm may rupture or dissect. Clinically, the criteria for surgical intervention are based on size and growth rate, but it remains difficult to identify a high-risk aneurysm, which may require intervention before the cutoff criteria, versus an aneurysm than can be treated safely by more conservative measures. In this work, we created a computational microstructural model of a medial lamellar unit (MLU) incorporating (1) growth and remodeling laws applied directly to discrete, individual fibers, (2) separate but interacting fiber networks for collagen, elastin, and smooth muscle, (3) active and passive smooth-muscle cell mechanics, and (4) failure mechanics for all three fiber types. The MLU model was then used to study different pathologies and microstructural anomalies that may play a role in vascular growth and failure. Our model recapitulated many aspects of arterial remodeling under hypertension with no underlying genetic syndrome including remodeling dynamics, tissue mechanics, and failure. Syndromic effects (smooth muscle cell (SMC) dysfunction or elastin fragmentation) drastically changed the simulated remodeling process, tissue behavior, and tissue strength. Different underlying pathologies were able to produce similarly dilatated vessels with different failure properties, providing a partial explanation for the imperfect nature of aneurysm size as a predictor of outcome.

Fig. 1

Aortic vessel geometry and repeated medial lamellar unit

Fig. 2

Computational model flowchart

Fig. 3

Mechanical behavior of fiber constituents

Fig. 4

(a) Circumferential stress evolution with normal blood pressure (100 mmHg) and hypertension (150 mmHg). (b) Overall tissue stretch evolution. (c) Fiber volume fraction evolution. (d) Growth contribution of stretch evolution. (e) Histogram of fiber stresses for each fiber type at t = 135 days and t = 300 days. (f) Elastic contribution of stretch evolution. Solid lines are means and the shaded region is 95% confidence interval for N = 8.

Fig. 5

Representative arterial networks and overall size during the remodeling process showing 3D network actin (gold), planar collagen (red), and planar elastin (black)

Fig. 6

Pooled histograms of all fibers in all networks (N = 8) for (a) fiber length evolution of actin and collagen. (b) Fiber radius evolution of actin and collagen. The arrows (green) show the actin fiber peak at small radii.

Fig. 7

Homeostatic hypertensive MLU showing small diameter(r < 25 μm) radial actin fibers (green), large diameter actinfibers(r > 25 μm) (gold), planar collagen (red), and planar elastin (black)

Fig. 8

Representative failure curves (black lines) and networks before (I) and after (II) failure for (a). circumferential failureand (b) shear failure. The dot shows the mean failure behavior and the cross shows the 95% confidence interval. The blue arrows on the networks show the direction of loading, and the dashed ovals show tear formation in (a), and delamination in (b).

Fig. 9

Material and failure properties for baseline normal blood pressure (left-hand bar, blue) and a 50% increase in baseline blood pressure (right-hand bar, yellow). Solid bars are means and the error bars are 95% confidence interval for N = 8. The symbol $†$ represents p < 0.05 and the symbol $‡$ represents p < 0.005 relative to the baseline vessel.

Fig. 10

(a) Circumferential stress evolution for contractility reduced to 25% of normal with no elastin removal. (b) Circumferential stress evolution for normal contractility with 30% elastin removal. (c) Circumferential stress evolution for contractility reduced to 25% of normal with 30% elastin removal. (d) Fiber volume fraction evolution for contractility reduced to 25% of normal with no elastin removal. (e) Fiber volume fraction evolution for normal contractility with 30% elastin removal. (f) Fiber volume fraction for contractility reduced to 25% of normal with 30% elastin removal. (g) MLU growth for contractility reduced to 25% of normal with no elastin removal. (h) MLU growth for normal contractility with 30% elastin removal. (i) MLU growth for contractility reduced to 25% of normal with 30% elastin removal. Solid lines are means and the shaded region is 95% confidence interval for N = 8.

Fig. 11

(a) Normalized material properties and (b) Normalized failure properties for baseline (blue), normal (100%) contractility with 30% removed elastin (orange), and 25% of normal contractility with normal elastin (0% removed) (gold). Solid bars are means and the error bars are 95% confidence interval for N = 8. The symbol $†$ represents p < 0.05 and the symbol $‡$ represents p < 0.005.

Fig. 12

Normalized homeostatic luminal diameter at load for all tested cases. The highlighted cases are within ±2.5% (dashed lines) of the mean for pathological growth cases. Circles are means and the error bars are the 95% confidence interval for N = 8.

Fig. 13

(a) Mechanical properties of baseline and pathological vessels. (b) Failure properties of baseline and pathological vessels. Solid bars are means and the error bars are 95% confidence interval for N = 8. The symbol $†$ represents p < 0.05 and the symbol $‡$ represents p < 0.005 relative to the baseline vessel.