Journal
INTERNATIONAL JOURNAL OF ENGINEERING SCIENCE
Volume 141, Issue -, Pages 35-46Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ijengsci.2019.05.014
Keywords
Wall stress; Blood pressure; Aorta; Constrained mixture; Inflammation
Categories
Funding
- US NIH [R01 HL105297, U01 HL116323, U01 HL142518, P01 HL134605]
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Uncontrolled hypertension is a major risk factor for myriad cardiovascular diseases. Among its many effects, hypertension increases central artery stiffness which in turn is both an initiator and indicator of disease. Despite extensive clinical, animal, and basic science studies, the biochemomechanical mechanisms by which hypertension drives aortic stiffening remain unclear. In this paper, we show that a new computational model of aortic growth and remodeling can capture differential effects of induced hypertension on the thoracic and abdominal aorta in a common mouse model of disease. Because the simulations treat the aortic wall as a constrained mixture of different constituents having different material properties and rates of turnover, one can gain increased insight into underlying constituent-level mechanisms of aortic remodeling. Model results suggest that the aorta can mechano-adapt locally to blood pressure elevation in the absence of marked inflammation, but large increases in inflammation drive a persistent maladaptive phenotype characterized primarily by adventitial fibrosis. Moreover, this fibrosis appears to occur via a marked increase in the rate of deposition of collagen having different material properties in the absence of a compensatory increase in the rate of matrix degradation. Controlling inflammation thus appears to be key to reducing fibrosis, but therapeutic strategies should not compromise the proteolytic activity of the wall that is essential to mechanical homeostasis. (C) 2019 Elsevier Ltd. All rights reserved.
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