0
Technical Brief

The Effect of Pentagalloyl Glucose on the Wall Mechanics and Inflammatory Activity of Rat Abdominal Aortic Aneurysms

[+] Author and Article Information
Mirunalini Thirugnanasambandam, Krysta L. Amezcua, Oluwaseun R. Adeyinka

UTSA/UTHSA Joint Graduate Program in Biomedical
Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249

Dan T. Simionescu

Department of Bioengineering,
Clemson University,
Clemson, SC 29634

Patricia G. Escobar

Department of Medicine,
University of Texas Health at San Antonio,
San Antonio, TX 78229

Eugene Sprague

UTSA/UTHSA Joint Graduate Program in Biomedical
Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249;
Department of Medicine,
University of Texas Health at San Antonio,
San Antonio, TX 78229

Beth Goins, Geoffrey D. Clarke

Department of Radiology,
University of Texas Health at San Antonio,
San Antonio, TX 78229

Hai-Chao Han

UTSA/UTHSA Joint Graduate Program in Biomedical
Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249;
Department of Mechanical Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249

Craig J. Goergen

Weldon School of Biomedical Engineering,
Purdue University,
West Lafayette, IN 47907

Ender Finol

UTSA/UTHSA Joint Graduate Program in Biomedical
Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249;
Department of Mechanical Engineering,
University of Texas at San Antonio,
San Antonio, TX 78249
e-mail: ender.finol@utsa.edu

1Corresponding author.

Manuscript received August 16, 2017; final manuscript received May 21, 2018; published online June 15, 2018. Assoc. Editor: Rouzbeh Amini.

J Biomech Eng 140(8), 084502 (Jun 15, 2018) (9 pages) Paper No: BIO-17-1368; doi: 10.1115/1.4040398 History: Received August 16, 2017; Revised May 21, 2018

An abdominal aortic aneurysm (AAA) is a permanent localized expansion of the abdominal aorta with mortality rate of up to 90% after rupture. AAA growth is a process of vascular degeneration accompanied by a reduction in wall strength and an increase in inflammatory activity. It is unclear whether this process can be intervened to attenuate AAA growth, and hence, it is of great clinical interest to develop a technique that can stabilize the AAA. The objective of this work is to develop a protocol for future studies to evaluate the effects of drug-based therapies on the mechanics and inflammation in rodent models of AAA. The scope of the study is limited to the use of pentagalloyl glucose (PGG) for aneurysm treatment in the calcium chloride rat AAA model. Peak wall stress (PWS) and matrix metalloproteinase (MMP) activity, which are the biomechanical and biological markers of AAA growth and rupture, were evaluated over 4 weeks in untreated and treated (with PGG) groups. The AAA specimens were mechanically characterized by planar biaxial tensile testing and the data fitted to a five-parameter nonlinear, hyperelastic, anisotropic Holzapfel–Gasser–Ogden (HGO) material model, which was used to perform finite element analysis (FEA) to evaluate PWS. Our results demonstrated that there was a reduction in PWS between pre- and post-AAA induction FEA models in the treatment group compared to the untreated group using either animal-specific or average material properties. However, this reduction was not statistically significant. Conversely, there was a statistically significant reduction in MMP-activated fluorescent signal between pre- and post-AAA induction models in the treated group compared to the untreated group. Therefore, the primary contribution of this work is the quantification of the stabilizing effects of PGG using biomechanical and biological markers of AAA, thus indicating that PGG could be part of a new clinical treatment strategy that will require further investigation.

FIGURES IN THIS ARTICLE
<>
Copyright © 2018 by ASME
Your Session has timed out. Please sign back in to continue.

References

Michel, J.-B. , Martin-Ventura, J.-L. , Egido, J. , Sakalihasan, N. , Treska, V. , Lindholt, J. , Allaire, E. , Thorsteinsdottir, U. , Cockerill, G. , and Swedenborg, J. , 2011, “Novel Aspects of the Pathogenesis of Aneurysms of the Abdominal Aorta in Humans,” Cardiovasc. Res., 90(1), pp. 18–27. [CrossRef] [PubMed]
Hellenthal, F. A. M. V. I. , Buurman, W. A. , Wodzig, W. K. W. H. , and Schurink, G. W. H. , 2009, “Biomarkers of AAA Progression—Part 1: Extracellular Matrix Degeneration,” Nat. Rev. Cardiol., 6(7), pp. 464–474. [CrossRef] [PubMed]
Hellenthal, F. A. M. V. I. , Buurman, W. A. , Wodzig, W. K. W. H. , and Schurink, G. W. H. , 2009, “Biomarkers of Abdominal Aortic Aneurysm Progression—Part 2: Inflammation,” Nat. Rev. Cardiol., 6(8), pp. 543–552. [CrossRef] [PubMed]
Nordon, I. M. , Hinchliffe, R. J. , Loftus, I. M. , and Thompson, M. M. , 2011, “Pathophysiology and Epidemiology of Abdominal Aortic Aneurysms,” Nat. Rev. Cardiol., 8(2), pp. 92–102. [CrossRef] [PubMed]
Dobrin, P. B. , Baker, W. H. , and Gley, W. C. , 1984, “Elastolytic and Collagenolytic Studies of Arteries: Implications for the Mechanical Properties of Aneurysms,” Arch. Surg., 119(4), pp. 405–409. [CrossRef] [PubMed]
Lysgaard Poulsen, J. , Stubbe, J. , and Lindholt, J. S. , 2016, “Animal Models Used to Explore Abdominal Aortic Aneurysms: A Systematic Review,” Eur. J. Vasc. Endovascular Surg., 52(4), pp. 487–499. [CrossRef]
Longo, G. M. , Xiong, W. , Greiner, T. C. , Zhao, Y. , Fiotti, N. , and Baxter, B. T. , 2002, “Matrix Metalloproteinases 2 and 9 Work in Concert to Produce Aortic Aneurysms," the,” J. Clin. Invest., 110(5), pp. 625–632. [CrossRef] [PubMed]
Vorp, D. A. , and van de Geest, J. P. , 2005, “Biomechanical Determinants of Abdominal Aortic Aneurysm Rupture,” Aeterioscler., Thromb., Vasc. Biol., 25(8), pp. 1558–1566. [CrossRef]
Fillinger, M. F. , Raghavan, M. L. , Marra, S. P. , Cronenwett, J. L. , and Kennedy, F. E. , 2002, “In Vivo Analysis of Mechanical Wall Stress and Abdominal Aortic Aneurysm Rupture Risk,” J. Vasc. Surg., 36(3), pp. 589–597. [CrossRef] [PubMed]
Speelman, L. , Bosboom, E. M. , Schurink, G. W. , Hellenthal, F. A. , Buth, J. , Breeuwer, M. , Jacobs, M. J. , and van de Vosse, F. N. , 2008, “Patient-Specific AAA Wall Stress Analysis: 99-Percentile Versus Peak Stress,” Eur. J. Vasc. Endovascular Surg., 36(6), pp. 668–76. [CrossRef]
Isenburg, J. C. , Simionescu, D. T. , Starcher, B. C. , and Vyavahare, N. R. , 2007, “Elastin Stabilization for Treatment of Abdominal Aortic Aneurysms,” Circulation, 115(13), pp. 1729–1737. [CrossRef] [PubMed]
Nosoudi, N. , Chowdhury, A. , Siclari, S. , Parasaram, V. , Karamched, S. , and Vyavahare, N. , 2016, “Systemic Delivery of Nanoparticles Loaded With Pentagalloyl Glucose Protects Elastic Lamina and Prevents Abdominal Aortic Aneurysm in Rats,” J. Cardiovasc. Trans. Res., 9(5–6), pp. 445–455. [CrossRef]
Goergen, C. J. , Azuma, J. , Barr, K. N. , Magdefessel, L. , Kallop, D. Y. , Gogineni, A. , Grewall, A. , Weimer, R. M. , Connolly, A. J. , Dalman, R. L. , Taylor, C. A. , Tsao, P. S. , and Greve, J. M. , 2011, “Influences of Aortic Motion and Curvature on Vessel Expansion in Murine Experimental Aneurysms,” Arterioscler. Thromb. Vasc. Biol., 31(2), pp. 270–279. [CrossRef] [PubMed]
Holzapfel, G. A. , Gasser, T. C. , and Ogden, R. W. , 2000, “A New Constitutive Framework for Arterial Wall Mechanics and a Comparative Study of Material Models,” J. Elasticity Phys. Sci. Solids, 61(1), pp. 1–48. [CrossRef]
Holzapfel, G. A. , Gasser, T. C. , and Ogden, R. W. , 2004, “Comparison of a Multi-Layer Structural Model for Arterial Walls With a Fung-Type Model, and Issues of Material Stability,” ASME J. Biomech. Eng., 126(2), pp. 264–275. [CrossRef]
Badel, P. , Avril, S. , Lessner, S. , and Sutton, M. , 2012, “Mechanical Identification of Layer-Specific Properties of Mouse Carotid Arteries Using 3D-DIC and a Hyperelastic Anisotropic Constitutive Model,” Comput. Methods Biomech. Biomed. Eng., 15(1), pp. 37–48. [CrossRef]
Mottahedi, M. , and Han, H.-C. , 2016, “Artery Buckling Analysis Using a Two-Layered Wall Model With Collagen Dispersion,” J. Mech. Behav. Biomed. Mater., 60, pp. 515–524. [CrossRef] [PubMed]
Shum, J. , dimartino, E. S. , Goldhammer, A. , Goldman, D. H. , Acker, L. C. , Pater, G. , Ng, J. H. , Martufi, G. , and Finol, E. A. , 2010, “Semiautomatic Vessel Wall Detection and Quantification of Wall Thickness in Computed Tomography Images of Human Abdominal Aortic Aneurysms,” Med. Phys., 37(2), pp. 638–648. [CrossRef] [PubMed]
Yamanouchi, D. , Morgan, S. , Stair, C. , Seedial, S. , Lengfeld, J. , Kent, K. C. , and Liu, B. , 2012, “Accelerated Aneurysmal Dilation Associated With Apoptosis and Inflammation in a Newly Developed Calcium Phosphate Rodent Abdominal Aortic Aneurysm Model,” J. Vasc. Surg., 56(2), pp. 455–461. [CrossRef] [PubMed]
Chiou, A. C. , Chiu, B. , and Pearce, W. H. , 2001, “Murine Aortic Aneurysm Produced by Periarterial Application of Calcium Chloride,” J. Surg. Res., 99(2), pp. 371–376. [CrossRef] [PubMed]
Xiong, W. , Knispel, R. , Mactaggart, J. , and Baxter, B. T. , 2006, “Effects of Tissue Inhibitor of Metalloproteinase 2 Deficiency on Aneurysm Formation,” J. Vasc. Surg., 44(5), pp. 1061–1066. [CrossRef] [PubMed]
Tamarina, N. A. , mcmillan, W. D. , Shively, V. P. , and Pearce, W. H. , 1997, “Expression of Matrix Metalloproteinases and Their Inhibitors in Aneurysms and Normal Aorta,” Surgery, 122(2), pp. 264–272. [CrossRef] [PubMed]
Nosoudi, N. , Chowdhury, A. , Siclari, S. , Kramched, S. , Parasaram, V. , Parrish, J. , Gerard, P. , and Vyavahare, N. , 2016, “Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy With EDTA- and PGG-Loaded Nanoparticles,” Theranostics, 6(11), pp. 1975–1987. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

Flowchart illustrating the processes involved in the biomechanical assessment of rat AAA specimens

Grahic Jump Location
Fig. 2

IVIS image showing location of ROIs and the corresponding flux in the damaged (infrarenal) and healthy (suprarenal) zones in a treated subject. The outline of the aorta is shown with dashed lines.

Grahic Jump Location
Fig. 3

Cauchy stress versus stretch in the circumferential and axial directions (a) in an exemplary AAA specimen. Experimentally evaluated Cauchy stress was compared to that predicted using the HGO material model parameters derived from the optimization algorithm (b) using pointwise-averaged material model parameters.

Grahic Jump Location
Fig. 4

Coronal view of the distribution of first principal stress (N/cm2) on the AAA wall of untreated ((a) and (b)) and treated ((c) and (d)) specimens pre-AAA ((a) and (c)) and post-AAA ((b) and (d)) induction surgery. (Orientation—A: anterior; P: posterior; H: head; and F: foot).

Grahic Jump Location
Fig. 5

(a) Percentage change in mean peak wall stress and (b) average (and standard error of the mean) percentage change in peak wall stress pre- and post-AAA induction surgery in untreated and treated groups while using average and subject-specific material model parameters

Grahic Jump Location
Fig. 6

IVIS images showing fluorescence maps representing MMP activity in an exemplary untreated (a) and treated (b) rat AAA. Warmer colors indicate higher flux, and hence, higher MMP activity. The outline of the aorta is shown with dashed lines in both subjects.

Grahic Jump Location
Fig. 7

Mean and corresponding standard error of mean values of MMP-based metrics derived from flux and radiance in untreated and treated subjects: (a) mean absolute values of flux and radiance, (b) mean ratio of flux and radiance in diseased and healthy ROIs, (c) mean ratio of flux and radiance in diseased and reference ROIs, and (d) mean ratio of normalized flux and radiance in diseased and healthy ROIs. Note that the absolute values of flux and radiance in the untreated group have been scaled down by a factor of 104.

Tables

Errata

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In