Modeling mechano-driven and immuno-mediated aortic maladaptation in hypertension
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Uncontrolled hypertension is a primary risk factor for diverse cardiovascular diseases and thus remains responsible for significant morbidity and mortality. Hypertension leads to marked changes in the composition, structure, properties, and function of central arteries; hence, there has long been interest in quantifying the associated wall mechanics. Indeed, over the past 20 years there has been increasing interest in formulating mathematical models of the evolving geometry and biomechanical behavior of central arteries that occur during hypertension. In this paper, we introduce a new mathematical model of growth (changes in mass) and remodeling (changes in microstructure) of the aortic wall for an animal model of induced hypertension that exhibits both mechano-driven and immuno-mediated matrix turnover. In particular, we present a bilayered model of the aortic wall to account for differences in medial versus adventitial growth and remodeling and we include mechanical stress and inflammatory cell density as determinants of matrix turnover. Using this approach, we can capture results from a recent report of adventitial fibrosis that resulted in marked aortic maladaptation in hypertension. We submit that this model can also be used to identify novel hypotheses to guide future experimentation.
KeywordsAorta Central artery Stiffness Growth Remodeling Inflammation
This work was supported, in part, by grants from the US NIH: R01 HL105297 (to C.A. Figueroa and J.D. Humphrey), U01 HL116323 (to J.D. Humphrey and G.E. Karniadakis), R01 HL128602 (to J.D. Humphrey, C.K. Breuer, and Y. Wang), P01 HL134605 (to G. Tellides and J.D. Humphrey via a PPG Award to D. Rifkin, NYU), and R03 EB021430 (to J.D. Humphrey); from the Ministerio de Educación, Cultura y Deporte of Spain: CAS17/00068 (to M. Latorre); and from Universidad Politécnica de Madrid: ‘Ayudas al personal docente e investigador para estancias breves en el extranjero 2017’ (to M. Latorre). Additional support was given to M. Latorre by grant DPI2015-69801-R from the Dirección General de Proyectos de Investigación, Ministerio de Economía y Competitividad of Spain (to F.J. Montáns and J.M. Benítez). ML gratefully acknowledges the support given by the Department of Biomedical Engineering, Yale University, during his postdoctoral stay.
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Conflict of interest
The authors declare that they have no conflict of interest.
- Durrant JR, Seals DR, Connell ML, Russell MJ, Lawson BR, Folian BJ, Donato AJ, Lesniewski LA (2009) Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J Physiol 587(13):3271–3285CrossRefGoogle Scholar
- Wu J, Saleh MA, Kirabo A, Itani HA, Montaniel KRC, Xiao L, Chen W, Mernaugh RL, Cai H, Bernstein KE, Goronzy JJ, Weyand CM, Curci JA, Barbaro NR, Moreno H, Davies SS, Roberts LJ, Madhur MS, Harrison DG (2016) Immune activation caused by vascular oxidation promotes fibrosis and hypertension. J Clin Investig 126(1):50–67CrossRefGoogle Scholar