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Research Papers

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

[+] Author and Article Information
J. S. Wilson

Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520

L. Virag, I. Karšaj

Faculty of Mechanical Engineering and Naval Architecture,
University of Zagreb,
10000 Zagreb, Croatia

P. Di Achille

Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520

J. D. Humphrey

Fellow ASME
Department of Biomedical Engineering,
Yale University,
New Haven, CT 06520;
Vascular Biology and Therapeutics Program,
Yale School of Medicine,
New Haven, CT 06520
e-mail: jay.humphrey@yale.edu

1Corresponding author. Present address: Department of Biomedical Engineering, Malone Engineering Center, Yale University, New Haven, CT 06520.

Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received November 13, 2012; final manuscript received January 14, 2013; accepted manuscript posted January 18, 2013; published online February 7, 2013. Editor: Victor H. Barocas.

J Biomech Eng 135(2), 021011 (Feb 07, 2013) (14 pages) Paper No: BIO-12-1552; doi: 10.1115/1.4023437 History: Received November 13, 2012; Revised January 14, 2013; Accepted January 18, 2013

Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.

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References

Humphrey, J. D., and Taylor, C. A., 2008, “Intracranial and Abdominal Aortic Aneurysms: Similarities, Differences, and Need for a New Class of Computational Models,” Annu. Rev. Biomed. Eng., 10, pp. 221–246. [CrossRef] [PubMed]
Humphrey, J. D., and Holzapfel, G. A., 2012, “Mechanics, Mechanobiology, and Modeling of Human Abdominal Aorta and Aneurysms,” J. Biomech., 45(5), pp. 805–814. [CrossRef] [PubMed]
Vorp, D. A., 2007, “Biomechanics of Abdominal Aortic Aneurysm,” J. Biomech., 40(9), pp. 1887–1902. [CrossRef] [PubMed]
Salsac, A. V., Sparks, S. R., and Lasheras, J. C., 2004, “Hemodynamic Changes Occurring During the Progressive Enlargement of Abdominal Aortic Aneurysms,” Ann. Vasc. Surg., 18(1), pp. 14–21. [CrossRef] [PubMed]
Salsac, A.-V., Sparks, S. R., Chomaz, J. M., and Lasheras, J. C., 2006, “Evolution of the Wall Shear Stresses During the Progressive Enlargement of Symmetric Abdominal Aortic Aneurysms,” J. Fluid Mech., 550, pp. 19–51. [CrossRef]
Bluestein, D., Niu, L., Schoephoerster, R. T., and Dewanjee, M. K., 1996, “Steady Flow in an Aneurysm Model: Correlation Between Fluid Dynamics and Blood Platelet Deposition,” J. Biomech. Eng., 118(3), pp. 280–286. [CrossRef] [PubMed]
Les, A. S., Shadden, S. C., Figueroa, C. A., Park, J. M., Tedesco, M. M., Herfkens, R. J., Dalman, R. L., and Taylor, C. A., 2010, “Quantification of Hemodynamics in Abdominal Aortic Aneurysms During Rest and Exercise Using Magnetic Resonance Imaging and Computational Fluid Dynamics,” Ann. Biomed. Eng., 38(4), pp. 1288–1313. [CrossRef] [PubMed]
O'Rourke, M. J., McCullough, J. P., and Kelly, S., 2012, “An Investigation of the Relationship Between Hemodynamics and Thrombus Deposition Within Patient-Specific Models of Abdominal Aortic Aneurysm,” Proc. Inst. Mech. Eng., Part H: J. Eng. Med., 226(7), pp. 548–564. [CrossRef]
Biasetti, J., Hussain, F., and Gasser, T. C., 2011, “Blood Flow and Coherent Vortices in the Normal and Aneurysmatic Aortas: A Fluid Dynamical Approach to Intra-Luminal Thrombus Formation,” J. R. Soc., Interface, 8(63), pp. 1449–1461. [CrossRef]
Arzani, A., and Shadden, S. C., 2012, “Characterization of the Transport Topology in Patient-Specific Abdominal Aortic Aneurysm Models,” Phys. Fluids, 24(8), p. 081901. [CrossRef]
Gersh, K. C., Nagaswami, C., and Weisel, J. W., 2009, “Fibrin Network Structure and Clot Mechanical Properties are Altered by Incorporation of Erythrocytes,” Thromb. Haemostasis, 102(6), pp. 1169–1175. [CrossRef]
Tong, J., Cohnert, T., Regitnig, P., and Holzapfel, G. A., 2011, “Effects of Age on the Elastic Properties of the Intraluminal Thrombus and the Thrombus-Covered Wall in Abdominal Aortic Aneurysms: Biaxial Extension Behaviour and Material Modelling,” Eur. J. Vasc. Endovasc. Surg., 42(2), pp. 207–219. [CrossRef] [PubMed]
Scott, D. J., Prasad, P., Philippou, H., Rashid, S. T., Sohrabi, S., Whalley, D., Kordowicz, A., Tang, Q., West, R. M., Johnson, A., Woods, J., Ajjan, R. A., and Ariëns, R. A., 2011, “Clot Architecture is Altered in Abdominal Aortic Aneurysms and Correlates With Aneurysm Size,” Arterioscler., Thromb., Vasc. Biol., 31(12), pp. 3004–3010. [CrossRef]
Takagi, H., Manabe, H., Kawai, N., Goto, S. N., and Umemoto, T., 2009, “Circulating Lipoprotein(a) Concentrations and Abdominal Aortic Aneurysm Presence,” Interact Cardiovasc. Thorac. Surg., 9(3), pp. 467–470. [CrossRef] [PubMed]
Pulinx, B., Hellenthal, F. A., Hamulyák, K., van Dieijen-Visser, M. P., Schurink, G. W., and Wodzig, W. K., 2011, “Differential Protein Expression in Serum of Abdominal Aortic Aneurysm Patients—A Proteomic Approach,” Eur. J. Vasc. Endovasc. Surg., 42(5), pp. 563–570. [CrossRef] [PubMed]
Mann, K. G., 2003, “Thrombin Formation,” Chest, 124(3 Suppl), pp. 4S–10S. [CrossRef] [PubMed]
Weisel, J. W., 2004, “The Mechanical Properties of Fibrin for Basic Scientists and Clinicians,” Biophys. Chem., 112(2–3), pp. 267–276. [CrossRef] [PubMed]
Weisel, J. W., 2007, “Structure of Fibrin: Impact on Clot Stability,” J. Thromb. Haemost., 5(Suppl 1), pp. 116–124. [CrossRef] [PubMed]
Furie, B., and Furie, B. C., 2007, “In Vivo Thrombus Formation,” J. Thromb. Haemost., 5(Suppl 1), pp. 12–17. [CrossRef] [PubMed]
Gersh, K. C., Edmondson, K. E., and Weisel, J. W., 2010, “Flow Rate and Fibrin Fiber Alignment,” J. Thromb. Haemost., 8(12), pp. 2826–2828. [CrossRef] [PubMed]
Varjú, I., Sótonyi, P., Machovich, R., Szabó, L., Tenekedjiev, K., Silva, M. M., Longstaff, C., and Kolev, K., 2011, “Hindered Dissolution of Fibrin Formed Under Mechanical Stress,” J. Thromb. Haemost., 9(5), pp. 979–986. [CrossRef] [PubMed]
Xu, Z., Kamocka, M., Alber, M., and Rosen, E. D., 2011, “Computational Approaches to Studying Thrombus Development,” Arterioscler., Thromb., Vasc. Biol., 31(3), pp. 500–505. [CrossRef]
Lobanov, A. I., and Starozhilova, T. K., 2005, “The Effect of Convective Flows on Blood Coagulation Processes,” Pathophysiol. Haemost. Thromb., 34(2–3), pp. 121–134. [CrossRef] [PubMed]
Anand, M., Rajagopal, K., and Rajagopal, K. R., 2005, “A Model for the Formation and Lysis of Blood Clots,” Pathophysiol. Haemost. Thromb., 34(2–3), pp. 109–120. [CrossRef] [PubMed]
Xu, Z., Chen, N., Kamocka, M. M., Rosen, E. D., and Alber, M., 2008, “A Multiscale Model of Thrombus Development,” J. R. Soc., Interface, 5(24), pp. 705–722. [CrossRef]
Xu, Z., Lioi, J., Mu, J., Kamocka, M. M., Liu, X., Chen, D. Z., Rosen, E. D., and Alber, M., 2010, “A Multiscale Model of Venous Thrombus Formation With Surface-Mediated Control of Blood Coagulation Cascade,” Biophys. J., 98(9), pp. 1723–1732. [CrossRef] [PubMed]
Biasetti, J., Spazzini, P. G., Swedenborg, J., and Gasser, T. C., 2012, “An Integrated Fluid-Chemical Model Toward Modeling the Formation of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms,” Front. Physiol., 3, pp. 266–270. [CrossRef] [PubMed]
Leiderman, K., and Fogelson, A. L., 2011, “Grow With the Flow: A Spatial-Temporal Model of Platelet Deposition and Blood Coagulation Under Flow,” Math. Med. Biol., 28(1), pp. 47–84. [CrossRef] [PubMed]
Scianna, M., and Preziosi, L., 2012, “Multiscale Developments of the Cellular Potts Model,” Multiscale Model. Simul., 10(2), pp. 342–382. [CrossRef]
Flamm, M. H., and Diamond, S. L., 2012, “Multiscale Systems Biology and Physics of Thrombosis Under Flow,” Ann. Biomed. Eng., 40(11), pp. 2355–2364. [CrossRef] [PubMed]
Basciano, C., Kleinstreuer, C., Hyun, S., and Finol, E. A., 2011, “A Relation Between Near-Wall Particle-Hemodynamics and Onset of Thrombus Formation in Abdominal Aortic Aneurysms,” Ann. Biomed. Eng., 39(7), pp. 2010–2026. [CrossRef] [PubMed]
Biasetti, J., Gasser, T. C., Auer, M., Hedin, U., and Labruto, F., 2010, “Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms With Emphasis on a Potential Thrombus Formation Mechanism,” Ann. Biomed. Eng., 38(2), pp. 380–390. [CrossRef] [PubMed]
van Dam, E. A., Dams, S. D., Peters, G. W., Rutten, M. C., Schurink, G. W., Buth, J., and van de Vosse, F. N., 2006, “Determination of Linear Viscoelastic Behavior of Abdominal Aortic Aneurysm Thrombus,” Biorheology, 43(6), pp. 695–707. [PubMed]
Brady, A. R., Thompson, S. G., Fowkes, F. G., Greenhalgh, R. M., and Powell, J. T., 2004, “Abdominal Aortic Aneurysm Expansion: Risk Factors and Time Intervals for Surveillance,” Circulation, 110(1), pp. 16–21. [CrossRef] [PubMed]
Kurvers, H., Veith, F. J., Lipsitz, E. C., Ohki, T., Gargiulo, N. J., Cayne, N. S., Suggs, W. D., Timaran, C. H., Kwon, G. Y., Rhee, S. J., and Santiago, C., 2004, “Discontinuous, Staccato Growth of Abdominal Aortic Aneurysms,” J. Am. Coll. Surg., 199(5), pp. 709–715. [CrossRef] [PubMed]
Wang, D. H., Makaroun, M., Webster, M. W., and Vorp, D. A., 2001, “Mechanical Properties and Microstructure of Intraluminal Thrombus From Abdominal Aortic Aneurysm,” J. Biomech. Eng., 123(6), pp. 536–539. [CrossRef] [PubMed]
Fontaine, V., Jacob, M. P., Houard, X., Rossignol, P., Plissonnier, D., Angles-Cano, E., and Michel, J. B., 2002, “Involvement of the Mural Thrombus as a Site of Protease Release and Activation in Human Aortic Aneurysms,” Am. J. Pathol., 161(5), pp. 1701–1710. [CrossRef] [PubMed]
Whittaker, P., and Przyklenk, K., 2009, “Fibrin Architecture in Clots: A Quantitative Polarized Light Microscopy Analysis,” Blood Cells Mol. Dis., 42(1), pp. 51–56. [CrossRef] [PubMed]
Adolph, R., Vorp, D. A., Steed, D. L., Webster, M. W., Kameneva, M. V., and Watkins, S. C., 1997, “Cellular Content and Permeability of Intraluminal Thrombus in Abdominal Aortic Aneurysm,” J. Vasc. Surg., 25(5), pp. 916–926. [CrossRef] [PubMed]
Di Martino, E., Mantero, S., Inzoli, F., Melissano, G., Astore, D., Chiesa, R., and Fumero, R., 1998, “Biomechanics of Abdominal Aortic Aneurysm in the Presence of Endoluminal Thrombus: Experimental Characterisation and Structural Static Computational Analysis,” Eur. J. Vasc. Endovasc. Surg., 15(4), pp. 290–299. [CrossRef] [PubMed]
van Dam, E. A., Dams, S. D., Peters, G. W., Rutten, M. C., Schurink, G. W., Buth, J., and van de Vosse, F. N., 2008, “Non-Linear Viscoelastic Behavior of Abdominal Aortic Aneurysm Thrombus,” Biomech. Model. Mechanobiol., 7(2), pp. 127–137. [CrossRef] [PubMed]
Georgakarakos, E., Ioannou, C. V., Kamarianakis, Y., Papaharilaou, Y., Kostas, T., Manousaki, E., and Katsamouris, A. N., 2010, “The Role of Geometric Parameters in the Prediction of Abdominal Aortic Aneurysm Wall Stress,” Eur. J. Vasc. Endovasc. Surg., 39(1), pp. 42–48. [CrossRef] [PubMed]
Speelman, L., Schurink, G. W., Bosboom, E. M., Buth, J., Breeuwer, M., van de Vosse, F. N., and Jacobs, M. H., 2010, “The Mechanical Role of Thrombus on the Growth Rate of an Abdominal Aortic Aneurysm,” J. Vasc. Surg., 51(1), pp. 19–26. [CrossRef] [PubMed]
Vorp, D. A., Mandarino, W. A., Webster, M. W., and Gorcsan, J., 1996, “Potential Influence of Intraluminal Thrombus on Abdominal Aortic Aneurysm as Assessed by a New Non-Invasive Method,” Cardiovasc. Surg., 4(6), pp. 732–739. [CrossRef] [PubMed]
Vande Geest, J. P., Sacks, M. S., and Vorp, D. A., 2006, “A Planar Biaxial Constitutive Relation for the Luminal Layer of Intra-Luminal Thrombus in Abdominal Aortic Aneurysms,” J. Biomech., 39(13), pp. 2347–2354. [CrossRef] [PubMed]
Ashton, J. H., Vande Geest, J. P., Simon, B. R., and Haskett, D. G., 2009, “Compressive Mechanical Properties of the Intraluminal Thrombus in Abdominal Aortic Aneurysms and Fibrin-Based Thrombus Mimics,” J. Biomech., 42(3), pp. 197–201. [CrossRef] [PubMed]
Fontaine, V., Touat, Z., Mtairag, E. M., Vranckx, R., Louedec, L., Houard, X., Andreassian, B., Sebbag, U., Palombi, T., Jacob, M. P., Meilhac, O., and Michel, J. B., 2004, “Role of Leukocyte Elastase in Preventing Cellular Re-Colonization of the Mural Thrombus,” Am. J. Pathol., 164(6), pp. 2077–2087. [CrossRef] [PubMed]
Swedenborg, J., and Eriksson, P., 2006, “The Intraluminal Thrombus as a Source of Proteolytic Activity,” Ann. N.Y. Acad. Sci., 1085, pp. 133–138. [CrossRef] [PubMed]
Houard, X., Touat, Z., Ollivier, V., Louedec, L., Philippe, M., Sebbag, U., Meilhac, O., Rossignol, P., and Michel, J. B., 2009, “Mediators of Neutrophil Recruitment in Human Abdominal Aortic Aneurysms,” Cardiovasc. Res., 82(3), pp. 532–541. [CrossRef] [PubMed]
Houard, X., Ollivier, V., Louedec, L., Michel, J. B., and Bäck, M., 2009, “Differential Inflammatory Activity Across Human Abdominal Aortic Aneurysms Reveals Neutrophil-Derived Leukotriene B4 as a Major Chemotactic Factor Released From the Intraluminal Thrombus,” FASEB J., 23(5), pp. 1376–1383. [CrossRef] [PubMed]
Michel, J. B., Martin-Ventura, J. L., Egido, J., Sakalihasan, N., Treska, V., Lindholt, J., Allaire, E., Thorsteinsdottir, U., Cockerill, G., Swedenborg, J., and FAD EU consortium, 2011, “Novel Aspects of the Pathogenesis of Aneurysms of the Abdominal Aorta in Humans,” Cardiovasc. Res., 90(1), pp. 18–27. [CrossRef] [PubMed]
Wiernicki, I., Stachowska, E., Safranow, K., Cnotliwy, M., Rybicka, M., Kaczmarczyk, M., and Gutowski, P., 2010, “Enhanced Matrix-Degrading Proteolytic Activity Within the Thin Thrombus-Covered Wall of Human Abdominal Aortic Aneurysms,” Atherosclerosis, 212(1), pp. 161–165. [CrossRef] [PubMed]
Touat, Z., Ollivier, V., Dai, J., Huisse, M. G., Bezeaud, A., Sebbag, U., Palombi, T., Rossignol, P., Meilhac, O., Guillin, M. C., and Michel, J. B., 2006, “Renewal of Mural Thrombus Releases Plasma Markers and is Involved in Aortic Abdominal Aneurysm Evolution,” Am. J. Pathol., 168(3), pp. 1022–1030. [CrossRef] [PubMed]
Houard, X., Leclercq, A., Fontaine, V., Coutard, M., Martin-Ventura, J.-L., Ho-Tin-Noe, B., Touat, Z., Meilhac, O., and Michel, J.-B., 2006, “Retention and Activation of Blood-Borne Proteases in the Arterial Wall: Implications for Atherothrombosis,” J. Am. Coll. Cardiol., 48(9), pp. A3–A9. [CrossRef]
Khan, J. A., Abdul Rahman, M. N., Mazari, F. A., Shahin, Y., Smith, G., Madden, L., Fagan, M. J., Greenman, J., McCollum, P. T., and Chetter, I. C., 2012, “Intraluminal Thrombus has a Selective Influence on Matrix Metalloproteinases and Their Inhibitors (Tissue Inhibitors of Matrix Metalloproteinases) in the Wall of Abdominal Aortic Aneurysms,” Ann. Vasc. Surg., 26(3), pp. 322–329. [CrossRef] [PubMed]
Folkesson, M., Silveira, A., Eriksson, P., and Swedenborg, J., 2011, “Protease Activity in the Multi-Layered Intra-Luminal Thrombus of Abdominal Aortic Aneurysms,” Atherosclerosis, 218(2), pp. 294–299. [CrossRef] [PubMed]
Freestone, T., Turner, R. J., Coady, A., Higman, D. J., Greenhalgh, R. M., and Powell, J. T., 1995, “Inflammation and Matrix Metalloproteinases in the Enlarging Abdominal Aortic Aneurysm,” Arterioscler., Thromb., Vasc. Biol., 15(8), pp. 1145–1151. [CrossRef]
Curci, J. A., Liao, S., Huffman, M. D., Shapiro, S. D., and Thompson, R. W., 1998, “Expression and Localization of Macrophage Elastase (Matrix Metalloproteinase-12) in Abdominal Aortic Aneurysms,” J. Clin. Invest., 102(11), pp. 1900–1910. [CrossRef] [PubMed]
Rizas, K. D., Ippagunta, N., and Tilson, M. D., 2009, “Immune Cells and Molecular Mediators in the Pathogenesis of the Abdominal Aortic Aneurysm,” Cardiol. Rev., 17(5), pp. 201–210. [CrossRef] [PubMed]
Siegel, C. L., Cohan, R. H., Korobkin, M., Alpern, M. B., Courneya, D. L., and Leder, R. A., 1994, “Abdominal Aortic Aneurysm Morphology: CT Features in Patients With Ruptured and Nonruptured Aneurysms,” AJR, Am. J. Roentgenol., 163(5), pp. 1123–1129. [CrossRef]
Schriefl, A. J., Collins, M. J., Pierce, D. M., Holzapfel, G. A., Niklason, L. E., and Humphrey, J. D., 2012, “Remodeling of Intramural Thrombus and Collagen in an Ang-II Infusion ApoE-/- Model of Dissecting Aortic Aneurysms,” Thromb. Res., 130(3), p. pp. 139–146. [CrossRef]
Houard, X., Rouzet, F., Touat, Z., Philippe, M., Dominguez, M., Fontaine, V., Sarda-Mantel, L., Meulemans, A., Le Guludec, D., Meilhac, O., and Michel, J. B., 2007, “Topology of the Fibrinolytic System Within the Mural Thrombus of Human Abdominal Aortic Aneurysms,” J. Pathol., 212(1), pp. 20–28. [CrossRef] [PubMed]
Carrell, T. W., Burnand, K. G., Booth, N. A., Humphries, J., and Smith, A., 2006, “Intraluminal Thrombus Enhances Proteolysis in Abdominal Aortic Aneurysms,” Vascular, 14(1), pp. 9–16. [CrossRef] [PubMed]
Knox, J. B., Sukhova, G. K., Whittemore, A. D., and Libby, P., 1997, “Evidence for Altered Balance Between Matrix Metalloproteinases and Their Inhibitors in Human Aortic Diseases,” Circulation, 95(1), pp. 205–212. [CrossRef] [PubMed]
Vorp, D. A., Lee, P. C., Wang, D. H., Makaroun, M. S., Nemoto, E. M., Ogawa, S., and Webster, M. W., 2001, “Association of Intraluminal Thrombus in Abdominal Aortic Aneurysm With Local Hypoxia and Wall Weakening,” J. Vasc. Surg., 34(2), pp. 291–299. [CrossRef] [PubMed]
Diehm, N., Di Santo, S., Schaffner, T., Schmidli, J., Völzmann, J., Jüni, P., Baumgartner, I., and Kalka, C., 2008, “Severe Structural Damage of the Seemingly Non-Diseased Infrarenal Aortic Aneurysm Neck,” J. Vasc. Surg., 48(2), pp. 425–434. [CrossRef] [PubMed]
Gong, Y., Hart, E., Shchurin, A., and Hoover-Plow, J., 2008, “Inflammatory Macrophage Migration Requires MMP-9 Activation by Plasminogen in Mice,” J. Clin. Invest., 118(9), pp. 3012–3024. [CrossRef] [PubMed]
Plow, E. F., and Hoover-Plow, J., 2004, “The Functions of Plasminogen in Cardiovascular Disease,” Trends Cardiovasc. Med., 14(5), pp. 180–186. [CrossRef] [PubMed]
Falcone, D. J., McCaffrey, T. A., Haimovitz-Friedman, A., Vergilio, J. A., and Nicholson, A. C., 1993, “Macrophage and Foam Cell Release of Matrix-Bound Growth Factors. Role of Plasminogen Activation,” J. Biol. Chem., 268(16), pp. 11951–11958. [PubMed]
Meilhac, O., Ho-Tin-Noé, B., Houard, X., Philippe, M., Michel, J. B., and Anglés-Cano, E., 2003, “Pericellular Plasmin Induces Smooth Muscle Cell Anoikis,” FASEB J., 17(10), pp. 1301–1303. [CrossRef] [PubMed]
Coutard, M., Touat, Z., Houard, X., Leclercq, A., and Michel, J. B., 2010, “Thrombus Versus Wall Biological Activities in Experimental Aortic Aneurysms,” J. Vasc. Res., 47(4), pp. 355–366. [CrossRef] [PubMed]
Antonicelli, F., Bellon, G., Debelle, L., and Hornebeck, W., 2007, “Elastin-Elastases and Inflamm-Aging,” Curr. Top. Dev. Biol., 79, pp. 99–155. [CrossRef] [PubMed]
Faisal Khan, K. M., Laurie, G. W., McCaffrey, T. A., and Falcone, D. J., 2002, “Exposure of Cryptic Domains in the Alpha 1-Chain of Laminin-1 by Elastase Stimulates Macrophages Urokinase and Matrix Metalloproteinase-9 Expression,” J. Biol. Chem., 277(16), pp. 13778–13786. [CrossRef] [PubMed]
Weitz, J. I., Leslie, B., and Ginsberg, J., 1991, “Soluble Fibrin Degradation Products Potentiate Tissue Plasminogen Activator-Induced Fibrinogen Proteolysis,” J. Clin. Invest., 87(3), pp. 1082–1090. [CrossRef] [PubMed]
Nackman, G. B., Karkowski, F. J., Halpern, V. J., Gaetz, H. P., and Tilson, M. D., 1997, “Elastin Degradation Products Induce Adventitial Angiogenesis in the Anidjar/Dobrin Rat Aneurysm Model,” Surgery, 122(1), pp. 39–44. [CrossRef] [PubMed]
Mäyränpää, M. I., Trosien, J. A., Fontaine, V., Folkesson, M., Kazi, M., Eriksson, P., Swedenborg, J., and Hedin, U., 2009, “Mast Cells Associate With Neovessels in the Media and Adventitia of Abdominal Aortic Aneurysms,” J. Vasc. Surg., 50(2), pp. 388–395. [CrossRef] [PubMed]
Chen, Z. L., and Strickland, S., 1997, “Neuronal Death in the Hippocampus is Promoted by Plasmin-Catalyzed Degradation of Laminin,” Cell, 91(7), pp. 917–925. [CrossRef] [PubMed]
Michel, J. B., Thaunat, O., Houard, X., Meilhac, O., Caligiuri, G., and Nicoletti, A., 2007, “Topological Determinants and Consequences of Adventitial Responses to Arterial Wall Injury,” Arterioscler., Thromb., Vasc. Biol., 27(6), pp. 1259–1268. [CrossRef]
Dal Canto, A. J., Swanson, P. E., O'Guin, A. K., Speck, S. H., and Virgin, H. W., 2001, “IFN-Gamma Action in the Media of the Great Elastic Arteries, a Novel Immunoprivileged Site,” J. Clin. Invest., 107(2), pp. R15–22. [CrossRef] [PubMed]
Burns, W. R., Wang, Y., Tang, P. C., Ranjbaran, H., Iakimov, A., Kim, J., Cuffy, M., Bai, Y., Pober, J. S., and Tellides, G., 2005, “Recruitment of CXCR3+ and CCR5+ T Cells and Production of Interferon-Gamma-Inducible Chemokines in Rejecting Human Arteries,” Am. J. Transplant., 5(6), pp. 1226–1236. [CrossRef] [PubMed]
Odekon, L. E., Blasi, F., and Rifkin, D. B., 1994, “Requirement for Receptor-Bound Urokinase in Plasmin-Dependent Cellular Conversion of Latent TGF-Beta to TGF-Beta,” J. Cell. Physiol., 158(3), pp. 398–407. [CrossRef] [PubMed]
Baxter, B. T., Davis, V. A., Minion, D. J., Wang, Y. P., Lynch, T. G., and McManus, B. M., 1994, “Abdominal Aortic Aneurysms are Associated With Altered Matrix Proteins of the Nonaneurysmal Aortic Segments,” J. Vasc. Surg., 19(5), pp. 797–802. [CrossRef] [PubMed]
Goodall, S., Crowther, M., Hemingway, D. M., Bell, P. R., and Thompson, M. M., 2001, “Ubiquitous Elevation of Matrix Metalloproteinase-2 Expression in the Vasculature of Patients With Abdominal Aneurysms,” Circulation, 104(3), pp. 304–309. [CrossRef] [PubMed]
Tilson, M. D., and Dang, C., 1981, “Generalized Arteriomegaly. A Possible Predisposition to the Formation of Abdominal Aortic Aneurysms,” Arch. Surg. (Chicago), 116(8), pp. 1030–1032. [CrossRef]
Iwamoto, T., Kimura, A., Nakai, T., Kanaya, K., and Ishimaru, S., 2004, “Implications of Carotid Arteriomegaly in Patients With Aortic Aneurysm,” J. Atheroscler. Thromb., 11(6), pp. 348–353. [CrossRef] [PubMed]
Ayyalasomayajula, A., Vande Geest, J. P., and Simon, B. R., 2010, “Porohyperelastic Finite Element Modeling of Abdominal Aortic Aneurysms,” J. Biomech. Eng., 132(10), p. 104502. [CrossRef] [PubMed]
Vande Geest, J. P., Simon, B. R., and Mortazavi, A., 2006, “Toward a Model for Local Drug Delivery in Abdominal Aortic Aneurysms,” Ann. N.Y. Acad. Sci., 1085, pp. 396–399. [CrossRef] [PubMed]
Daugherty, A., Manning, M. W., and Cassis, L. A., 2000, “Angiotensin II Promotes Atherosclerotic Lesions and Aneurysms in Apolipoprotein E-Deficient Mice,” J. Clin. Invest., 105(11), pp. 1605–1612. [CrossRef] [PubMed]
Anidjar, S., Salzmann, J. L., Gentric, D., Lagneau, P., Camilleri, J. P., and Michel, J. B., 1990, “Elastase-Induced Experimental Aneurysms in Rats,” Circulation, 82(3), pp. 973–981. [CrossRef] [PubMed]
Eliason, J. L., Hannawa, K. K., Ailawadi, G., Sinha, I., Ford, J. W., Deogracias, M. P., Roelofs, K. J., Woodrum, D. T., Ennis, T. L., Henke, P. K., Stanley, J. C., Thompson, R. W., and Upchurch, G. R., 2005, “Neutrophil Depletion Inhibits Experimental Abdominal Aortic Aneurysm Formation,” Circulation, 112(2), pp. 232–240. [CrossRef] [PubMed]
Dai, J., Louedec, L., Philippe, M., Michel, J. B., and Houard, X., 2009, “Effect of Blocking Platelet Activation With AZD6140 on Development of Abdominal Aortic Aneurysm in a Rat Aneurysmal Model,” J. Vasc. Surg., 49(3), pp. 719–727. [CrossRef] [PubMed]
Hannawa, K. K., Eliason, J. L., Woodrum, D. T., Pearce, C. G., Roelofs, K. J., Grigoryants, V., Eagleton, M. J., Henke, P. K., Wakefield, T. W., Myers, D. D., Stanley, J. C., and Upchurch, G. R., 2005, “L-Selectin-Mediated Neutrophil Recruitment in Experimental Rodent Aneurysm Formation,” Circulation, 112(2), pp. 241–247. [CrossRef] [PubMed]
Pagano, M. B., Bartoli, M. A., Ennis, T. L., Mao, D., Simmons, P. M., Thompson, R. W., and Pham, C. T., 2007, “Critical Role of Dipeptidyl Peptidase I in Neutrophil Recruitment During the Development of Experimental Abdominal Aortic Aneurysms,” Proc. Natl. Acad. Sci. U.S.A., 104(8), pp. 2855–2860. [CrossRef] [PubMed]
Deng, G. G., Martin-McNulty, B., Sukovich, D. A., Freay, A., Halks-Miller, M., Thinnes, T., Loskutoff, D. J., Carmeliet, P., Dole, W. P., and Wang, Y. X., 2003, “Urokinase-Type Plasminogen Activator Plays a Critical Role in Angiotensin II-Induced Abdominal Aortic Aneurysm,” Circ. Res., 92(5), pp. 510–517. [CrossRef] [PubMed]
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,” J. Clin. Invest., 110(5), pp. 625–632. [CrossRef] [PubMed]
Longo, G. M., Buda, S. J., Fiotta, N., Xiong, W., Griener, T., Shapiro, S., and Baxter, B. T., 2005, “MMP-12 has a Role in Abdominal Aortic Aneurysms in Mice,” Surgery, 137(4), pp. 457–462. [CrossRef] [PubMed]
Allaire, E., Hasenstab, D., Kenagy, R. D., Starcher, B., Clowes, M. M., and Clowes, A. W., 1998, “Prevention of Aneurysm Development and Rupture by Local Overexpression of Plasminogen Activator Inhibitor-1,” Circulation, 98(3), pp. 249–255. [CrossRef] [PubMed]
Allaire, E., Forough, R., Clowes, M., Starcher, B., and Clowes, A. W., 1998, “Local Overexpression of TIMP-1 Prevents Aortic Aneurysm Degeneration and Rupture in a Rat Model,” J. Clin. Invest., 102(7), pp. 1413–1420. [CrossRef] [PubMed]
Grigoryants, V., Hannawa, K. K., Pearce, C. G., Sinha, I., Roelofs, K. J., Ailawadi, G., Deatrick, K. B., Woodrum, D. T., Cho, B. S., Henke, P. K., Stanley, J. C., Eagleton, M. J., and Upchurch, G. R., 2005, “Tamoxifen Up-Regulates Catalase Production, Inhibits Vessel Wall Neutrophil Infiltration, and Attenuates Development of Experimental Abdominal Aortic Aneurysms,” J. Vasc. Surg., 41(1), pp. 108–114. [CrossRef] [PubMed]
Kazi, M., Thyberg, J., Religa, P., Roy, J., Eriksson, P., Hedin, U., and Swedenborg, J., 2003, “Influence of Intraluminal Thrombus on Structural and Cellular Composition of Abdominal Aortic Aneurysm Wall,” J. Vasc. Surg., 38(6), pp. 1283–1292. [CrossRef] [PubMed]
Kazi, M., Zhu, C., Roy, J., Paulsson-Berne, G., Hamsten, A., Swedenborg, J., Hedin, U., and Eriksson, P., 2005, “Difference in Matrix-Degrading Protease Expression and Activity Between Thrombus-Free and Thrombus-Covered Wall of Abdominal Aortic Aneurysm,” Arterioscler., Thromb., Vasc. Biol., 25(7), pp. 1341–1346. [CrossRef]
Stenbaek, J., Kalin, B., and Swedenborg, J., 2000, “Growth of Thrombus may be a Better Predictor of Rupture Than Diameter in Patients With Abdominal Aortic Aneurysms,” Eur. J. Vasc. Endovasc. Surg., 20(5), pp. 466–469. [CrossRef] [PubMed]
Hans, S. S., Jareunpoon, O., Balasubramaniam, M., and Zelenock, G. B., 2005, “Size and Location of Thrombus in Intact and Ruptured Abdominal Aortic Aneurysms,” J. Vasc. Surg., 41(4), pp. 584–588. [CrossRef] [PubMed]
Vorp, D. A., and Vande Geest, J. P., 2005, “Biomechanical Determinants of Abdominal Aortic Aneurysm Rupture,” Arterioscler. Thromb. Vasc. Biol., 25(8), pp. 1558–1566. [CrossRef] [PubMed]
Sun, N., Leung, J. H., Wood, N. B., Hughes, A. D., Thom, S. A., Cheshire, N. J., and Xu, X. Y., 2009, “Computational Analysis of Oxygen Transport in a Patient-Specific Model of Abdominal Aortic Aneurysm With Intraluminal Thrombus,” Br. J. Radiol., 82(1), pp. S18–23. [CrossRef] [PubMed]
Yoshimura, K., Ikeda, Y., and Aoki, H., 2011, “Innocent Bystander? Intraluminal Thrombus in Abdominal Aortic Aneurysm,” Atherosclerosis, 218(2), pp. 285–286. [CrossRef] [PubMed]
Satoh, H., Nakamura, M., Satoh, M., Nakajima, T., Izumoto, H., Maesawa, C., Kawazoe, K., Masuda, T., and Hiramori, K., 2004, “Expression and Localization of Tumour Necrosis Factor-Alpha and its Converting Enzyme in Human Abdominal Aortic Aneurysm,” Clin. Sci., 106(3), pp. 301–306. [CrossRef] [PubMed]
Li, Z. Y., Sadat, U., U-King-Im, J., Tang, T. Y., Bowden, D. J., Hayes, P. D., and Gillard, J. H., 2010, “Association Between Aneurysm Shoulder Stress and Abdominal Aortic Aneurysm Expansion: A Longitudinal Follow-Up Study,” Circulation, 122(18), pp. 1815–1822. [CrossRef] [PubMed]
Wilson, J. S., Baek, S., and Humphrey, J. D., 2012, “Importance of Initial Aortic Properties on the Evolving Regional Anisotropy, Stiffness and Wall Thickness of Human Abdominal Aortic Aneurysms,” J. R. Soc., Interface, 9(74), pp. 2047–2058. [CrossRef]
Wilson, J. S., Baek, S., and Humphrey, J. D., 2013, “Parametric Study of Effects of Collagen Turnover on the Natural History of Abdominal Aortic Aneurysms,” Proc. R. Soc. London, Ser. A, 469(2150), (ePub ahead of print). [CrossRef]
Inzoli, F., Boschetti, F., Zappa, M., Longo, T., and Fumero, R., 1993, “Biomechanical Factors in Abdominal Aortic Aneurysm Rupture,” Eur. J. Vasc. Surg., 7(6), pp. 667–674. [CrossRef] [PubMed]
Mower, W. R., Quiñones, W. J., and Gambhir, S. S., 1997, “Effect of Intraluminal Thrombus on Abdominal Aortic Aneurysm Wall Stress,” J. Vasc. Surg., 26(4), pp. 602–608. [CrossRef] [PubMed]
Wang, D. H., Makaroun, M. S., Webster, M. W., and Vorp, D. A., 2002, “Effect of Intraluminal Thrombus on Wall Stress in Patient-Specific Models of Abdominal Aortic Aneurysm,” J. Vasc. Surg., 36(3), pp. 598–604. [CrossRef] [PubMed]
Maier, A., Gee, M. W., Reeps, C., Pongratz, J., Eckstein, H. H., and Wall, W. A., 2010, “A Comparison of Diameter, Wall Stress, and Rupture Potential Index for Abdominal Aortic Aneurysm Rupture Risk Prediction,” Ann. Biomed. Eng., 38(10), pp. 3124–3134. [CrossRef] [PubMed]
Gasser, T. C., Auer, M., Labruto, F., Swedenborg, J., and Roy, J., 2010, “Biomechanical Rupture Risk Assessment of Abdominal Aortic Aneurysms: Model Complexity Versus Predictability of Finite Element Simulations,” Eur. J. Vasc. Endovasc. Surg., 40(2), pp. 176–185. [CrossRef] [PubMed]
Larsson, E., Labruto, F., Gasser, T. C., Swedenborg, J., and Hultgren, R., 2011, “Analysis of Aortic Wall Stress and Rupture Risk in Patients With Abdominal Aortic Aneurysm With a Gender Perspective,” J. Vasc. Surg., 54(2), pp. 295–299. [CrossRef] [PubMed]
Ene, F., Gachon, C., Delassus, P., Carroll, R., Stefanov, F., O'Flynn, P., and Morris, L., 2011, “In Vitro Evaluation of the Effects of Intraluminal Thrombus on Abdominal Aortic Aneurysm Wall Dynamics,” Med. Eng. Phys., 33(8), pp. 957–966. [CrossRef] [PubMed]
Meyer, C. A., Guivier-Curien, C., and Moore, J. E., 2010, “Trans-Thrombus Blood Pressure Effects in Abdominal Aortic Aneurysms,” J. Biomech. Eng., 132(7), p. 071005. [CrossRef] [PubMed]
Schurink, G. W., van Baalen, J. M., Visser, M. J., and van Bockel, J. H., 2000, “Thrombus Within an Aortic Aneurysm Does not Reduce Pressure on the Aneurysmal Wall,” J. Vasc. Surg., 31(3), pp. 501–506. [CrossRef] [PubMed]
Brown, A. E., Litvinov, R. I., Discher, D. E., Purohit, P. K., and Weisel, J. W., 2009, “Multiscale Mechanics of Fibrin Polymer: Gel Stretching With Protein Unfolding and Loss of Water,” Science, 325(5941), pp. 741–744. [CrossRef] [PubMed]
Truijers, M., Fillinger, M. F., Renema, K. W., Marra, S. P., Oostveen, L. J., Kurvers, H. A., Schultzekool, L. J., and Blankensteijn, J. D., 2009, “In-Vivo Imaging of Changes in Abdominal Aortic Aneurysm Thrombus Volume During the Cardiac Cycle,” J. Endovasc. Ther., 16(3), pp. 314–319. [CrossRef] [PubMed]
Vande Geest, J. P., Di Martino, E. S., Bohra, A., Makaroun, M. S., and Vorp, D. A., 2006, “A Biomechanics-Based Rupture Potential Index for Abdominal Aortic Aneurysm Risk Assessment: Demonstrative Application,” Ann. N.Y. Acad. Sci., 1085, pp. 11–21. [CrossRef] [PubMed]
Gasser, T. C., Görgülü, G., Folkesson, M., and Swedenborg, J., 2008, “Failure Properties of Intraluminal Thrombus in Abdominal Aortic Aneurysm Under Static and Pulsating Mechanical Loads,” J. Vasc. Surg., 48(1), pp. 179–188. [CrossRef] [PubMed]
Labruto, F., Blomqvist, L., and Swedenborg, J., 2011, “Imaging the Intraluminal Thrombus of Abdominal Aortic Aneurysms: Techniques, Findings, and Clinical Implications,” J. Vasc. Interv. Radiol., 22(8), pp. 1069–1075. [CrossRef] [PubMed]
Nchimi, A., Defawe, O., Brisbois, D., Broussaud, T. K., Defraigne, J. O., Magotteaux, P., Massart, B., Serfaty, J. M., Houard, X., Michel, J. B., and Sakalihasan, N., 2010, “MR Imaging of Iron Phagocytosis in Intraluminal Thrombi of Abdominal Aortic Aneurysms in Humans,” Radiology, 254(3), pp. 973–981. [CrossRef] [PubMed]
Richards, J. M., Semple, S. I., MacGillivray, T. J., Gray, C., Langrish, J. P., Williams, M., Dweck, M., Wallace, W., McKillop, G., Chalmers, R. T., Garden, O. J., and Newby, D. E., 2011, “Abdominal Aortic Aneurysm Growth Predicted by Uptake of Ultrasmall Superparamagnetic Particles of Iron Oxide: A Pilot Study,” Circ. Cardiovasc. Imaging, 4(3), pp. 274–281. [CrossRef] [PubMed]
Watton, P. N., Hill, N. A., and Heil, M., 2004, “A Mathematical Model for the Growth of the Abdominal Aortic Aneurysm,” Biomech. Model. Mechanobiol., 3(2), pp. 98–113. [CrossRef] [PubMed]
Humphrey, J. D., and Rajagopal, K. R., 2003, “A Constrained Mixture Model for Arterial Adaptations to a Sustained Step Change in Blood Flow,” Biomech. Model. Mechanobiol., 2(2), pp. 109–126. [CrossRef] [PubMed]
Watton, P. N., Raberger, N. B., Holzapfel, G. A., and Ventikos, Y., 2009, “Coupling the Hemodynamic Environment to the Evolution of Cerebral Aneurysms: Computational Framework and Numerical Examples,” J. Biomech. Eng., 131(10), p. 101003. [CrossRef] [PubMed]
Zeinali-Davarani, S., Sheidaei, A., and Baek, S., 2011, “A Finite Element Model of Stress-Mediated Vascular Adaptation: Application to Abdominal Aortic Aneurysms,” Comput. Methods Biomech. Biomed. Eng., 14(9), pp. 803–817. [CrossRef]
Sheidaei, A., Hunley, S. C., Zeinali-Davarani, S., Raguin, L. G., and Baek, S., 2011, “Simulation of Abdominal Aortic Aneurysm Growth With Updating Hemodynamic Loads Using a Realistic Geometry,” Med. Eng. Phys., 33(1), pp. 80–88. [CrossRef] [PubMed]
Karšaj, I., and Humphrey, J. D., 2009, “A Mathematical Model of Evolving Mechanical Properties of Intraluminal Thrombus,” Biorheology, 46(6), pp. 509–527. [CrossRef] [PubMed]

Figures

Grahic Jump Location
Fig. 1

Patient's AAA volume history. Note the changes in volume of the lumen, ILT (thrombus), and aneurysmal sac over time, with a possible discrete deposition of thrombus between Jun. 2005 and Mar. 2006. From Basciano et al. [31], with kind permission from Springer Science and Business Media.

Grahic Jump Location
Fig. 2

Gross and ultrastructural appearance of a layered intraluminal thrombus from a human AAA. Note the entrapped cells in the luminal thrombus. From Wang et al. [36], with permission.

Grahic Jump Location
Fig. 3

Maximum tangential moduli of ILT from human AAAs separated by luminal (L), medial (M), and adventitial (A) layers and phase (a proposed indicator of age; see Fig. 4). From Tong et al. [12], with permission.

Grahic Jump Location
Fig. 4

Proposed histological phases of ILT maturation. From Tong et al. [12], with permission.

Grahic Jump Location
Fig. 5

Note the “crescent sign” on a contrast-enhanced CT study of a 59 year-old male with an AAA. (Left—axial image; Right—maximum-intensity projection reconstruction on an oblique sagittal projection). From Labruto et al. [124], with permission.

Grahic Jump Location
Fig. 6

Top: Simplified schema of the possible formation of a layered “space filling” ILT by multiple cycles of AAA sac enlargement and ILT deposition secondary to disturbed flow. Note that the specific initiation site in 3 is merely schematic. Bottom: Cross-sectional view at two different axial locations at one instant, when the luminal ILT layer (black) may remain in contact with the wall at the shoulder region while being distant from the anterior wall at the apex of the lesion. (Diagram by Carolyn Valentín).

Grahic Jump Location
Fig. 7

Comparison of a contrast-enhanced CT image (left) and a T2-weighted MR image (right) of an AAA in a 49 year-old male. Note the clear layers of the ILT evident in the MRI that are not delineated by CT. From Labruto et al. [124], with permission.

Grahic Jump Location
Fig. 8

Schema of some of the primary effectors governing the evolution of the mechanics of both the ILT and aneurysmal wall. Solid black arrow – “increases the amount/activity,” dotted black line—“degrades,” dashed gray line—“modulates the effect.” (ILT: intraluminal thrombus, SMC: smooth muscle cell, FB: fibroblast, WBC: white blood cell, RBC: red blood cell).

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