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Mechanical Characterization of the Lamellar Structure of Human Abdominal Aorta in the Development of Atherosclerosis: An Atomic Force Microscopy Study

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Abstract

Atherosclerosis is a major risk factor for cardiovascular disease. However, mechanisms of interaction of atherosclerotic plaque development and local stiffness of the lamellar structure of the arterial wall are not well established. In the current study, the local Young’s modulus of the wall and plaque components were determined for three different groups of healthy, mildly diseased and advanced atherosclerotic human abdominal aortas. Histological staining was performed to highlight the atherosclerotic plaque components and lamellar structure of the aortic media, consisting of concentric layers of elastin and interlamellar zones. The force spectroscopy mode of the atomic force microscopy was utilized to determine Young’s moduli of aortic wall lamellae and plaque components at the micron level. The high variability of Young’s moduli (E) at different locations of the atherosclerotic plaque such as the fibrous cap (E = 15.5± 2.6 kPa), calcification zone (E = 103.7±19.5 kPa), and lipid pool (E = 3.5±1.2 kPa) were observed. Reduction of elastin lamellae stiffness (18.6%), as well as stiffening of interlamellar zones (50%), were detected in the diseased portion of the medial layer of abdominal aortic wall compared to the healthy artery. Additionally, significant differences in the stiffness of both elastin lamellae and interlamellar zones were observed between the diseased wall and disease-free wall in incomplete plaques. Our results elucidate the alternation of the stiffness of different lamellae in the human abdominal aortic wall with atherosclerotic plaque development and may provide new insight on the remodeling of the aortic wall during the progression of atherosclerosis.

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References

  1. Akhtar, R. In vitro characterisation of arterial stiffening: from the macro-to the nano-scale. Artery Res. 8(1):1–8, 2014.

    Article  MathSciNet  Google Scholar 

  2. Akhtar, R., H. Graham, B. Derby, M. Sherratt, A. Trafford, R. Chadwick, et al. Frequency-modulated atomic force microscopy localises viscoelastic remodelling in the ageing sheep aorta. J. Mech. Behav. Biomed. Mater. 64:10–17, 2016.

    Article  Google Scholar 

  3. Akyildiz, A. C., L. Speelman, and F. J. Gijsen. Mechanical properties of human atherosclerotic intima tissue. J. Biomech. 47(4):773–783, 2014.

    Article  Google Scholar 

  4. Apostolakis, I. Z., S. D. Nandlall, and E. E. Konofagou. Piecewise pulse wave imaging (pPWI) for detection and monitoring of focal vascular disease in murine aortas and carotids in vivo. IEEE Trans. Med. Imaging 35(1):13–28, 2016.

    Article  Google Scholar 

  5. Avolio, A. Arterial stiffness. Pulse 1(1):14–28, 2013.

    Article  Google Scholar 

  6. Avolio, A., D. Jones, and M. Tafazzoli-Shadpour. Quantification of alterations in structure and function of elastin in the arterial media. Hypertension 32(1):170–175, 1998.

    Article  Google Scholar 

  7. Brüel, A., G. Ørtoft, and H. Oxlund. Inhibition of cross-links in collagen is associated with reduced stiffness of the aorta in young rats. Atherosclerosis. 140(1):135–145, 1998.

    Article  Google Scholar 

  8. Buchanan, J., C. Kleinstreuer, S. Hyun, and G. Truskey. Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta. J. Biomech. 36(8):1185–1196, 2003.

    Article  Google Scholar 

  9. Burke, A. P., and F. Tavora. Practical cardiovascular pathology. Philadelphia: Lippincott Williams & Wilkins, 2010.

    Google Scholar 

  10. Butt, H.-J., B. Cappella, and M. Kappl. Force measurements with the atomic force microscope: technique, interpretation and applications. Surf. Sci. Rep. 59(1–6):1–152, 2005.

    Article  Google Scholar 

  11. Cattell, M. A., J. C. Anderson, and P. S. Hasleton. Age-related changes in amounts and concentrations of collagen and elastin in normotensive human thoracic aorta. Clin. Chim. Acta 245(1):73–84, 1996.

    Article  Google Scholar 

  12. Chai, C.-K., L. Speelman, C. W. Oomens, and F. P. Baaijens. Compressive mechanical properties of atherosclerotic plaques—indentation test to characterise the local anisotropic behaviour. J. Biomech. 47(4):784–792, 2014.

    Article  Google Scholar 

  13. Discher, D. E., P. Janmey, and Y.-L. Wang. Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143, 2005.

    Article  Google Scholar 

  14. Doran, A. C., N. Meller, and C. A. McNamara. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 28(5):812–819, 2008.

    Article  Google Scholar 

  15. Ebenstein, D. M., D. Coughlin, J. Chapman, C. Li, and L. A. Pruitt. Nanomechanical properties of calcification, fibrous tissue, and hematoma from atherosclerotic plaques. J. Biomed. Mater. Res. Part A 91(4):1028–1037, 2009.

    Article  Google Scholar 

  16. Ethier, C. R., and C. A. Simmons. Introductory biomechanics: from cells to organisms. Cambridge: Cambridge University Press, 2007.

    Book  Google Scholar 

  17. Fischer, A. H., K. A. Jacobson, J. Rose, and R. Zeller. Hematoxylin and eosin staining of tissue and cell sections. Cold Spring Harb. Protoc. 2008. https://doi.org/10.1101/pdb.prot4986.

    Article  Google Scholar 

  18. Fukui, T., T. Matsumoto, T. Tanaka, T. Ohashi, K. Kumagai, H. Akimoto, et al. In vivo mechanical properties of thoracic aortic aneurysmal wall estimated from in vitro biaxial tensile test. Biomed. Mater. Eng. 15(4):295–305, 2004.

    Google Scholar 

  19. Glagov, S., D. Rowley, and R. Kohut. Atherosclerosis of human aorta and its coronary and renal arteries. A consideration of some hemodynamic factors which may be related to the marked differences in atherosclerotic involvement of the coronary and renal arteries. Arch Pathol. 72:558, 1961.

    Google Scholar 

  20. Haghighipour, N., M. Tafazzoli-Shadpour, and A. Avolio. Residual stress distribution in a lamellar model of the arterial wall. J. Med. Eng. Technol. 34(7–8):422–428, 2010.

    Article  Google Scholar 

  21. Hayenga, H., A. Trache, J. Trzeciakowski, and J. Humphrey. Regional atherosclerotic plaque properties in ApoE−/− mice quantified by atomic force, immunofluorescence, and light microscopy. J. Vasc. Res. 48(6):495–504, 2011.

    Article  Google Scholar 

  22. Holzapfel, G. A., G. Sommer, and P. Regitnig. Anisotropic mechanical properties of tissue components in human atherosclerotic plaques. J. Biomech. Eng. 126(5):657–665, 2004.

    Article  Google Scholar 

  23. Hutter, J. L., and J. Bechhoefer. Calibration of atomic-force microscope tips. Rev. Sci. Instrum. 64(7):1868–1873, 1993.

    Article  Google Scholar 

  24. Huynh, J., N. Nishimura, K. Rana, J. M. Peloquin, J. P. Califano, C. R. Montague, et al. Age-related intimal stiffening enhances endothelial permeability and leukocyte transmigration. Sci. Transl. Med. 3(112):112ra122, 2011.

    Article  Google Scholar 

  25. Imura, T., K. Yamamoto, T. Satoh, T. Mikami, and H. Yasuda. Arteriosclerotic change in the human abdominal aorta in vivo in relation to coronary heart disease and risk factors. Atherosclerosis. 73(2):149–155, 1988.

    Article  Google Scholar 

  26. Kamenskiy, A. V., Y. A. Dzenis, S. A. J. Kazmi, M. A. Pemberton, I. I. Pipinos, N. Y. Phillips, et al. Biaxial mechanical properties of the human thoracic and abdominal aorta, common carotid, subclavian, renal and common iliac arteries. Biomech. Model. Mechanobiol. 13(6):1341–1359, 2014.

    Article  Google Scholar 

  27. Kasas, S., G. Longo, and G. Dietler. Mechanical properties of biological specimens explored by atomic force microscopy. J. Phys. D Appl. Phys. 46(13):133001, 2013.

    Article  Google Scholar 

  28. Korshunov, V. A., S. M. Schwartz, and B. C. Berk. Vascular remodeling. Arterioscler. Thromb. Vasc. Biol. 27(8):1722–1728, 2007.

    Article  Google Scholar 

  29. Last, J. A., S. J. Liliensiek, P. F. Nealey, and C. J. Murphy. Determining the mechanical properties of human corneal basement membranes with atomic force microscopy. J. Struct. Biol. 167(1):19–24, 2009.

    Article  Google Scholar 

  30. Lekka, M., D. Gil, K. Pogoda, J. Dulińska-Litewka, R. Jach, J. Gostek, et al. Cancer cell detection in tissue sections using AFM. Arch. Biochem. Biophys. 518(2):151–156, 2012.

    Article  Google Scholar 

  31. Lundkvist, A., E. Lilleodden, W. Siekhaus, J. Kinney, L. Pruitt, and M. Balooch. Viscoelastic properties of healthy human artery measured in saline solution by AFM-based indentation technique. MRS Online Proc. Library Arch. 436:353, 1996.

    Article  Google Scholar 

  32. Maher, E., A. Creane, S. Sultan, N. Hynes, C. Lally, and D. J. Kelly. Tensile and compressive properties of fresh human carotid atherosclerotic plaques. J. Biomech. 42(16):2760–2767, 2009.

    Article  Google Scholar 

  33. Matsumoto, T., T. Goto, T. Furukawa, and M. Sato. Residual stress and strain in the lamellar unit of the porcine aorta: experiment and analysis. J. Biomech. 37(6):807–815, 2004.

    Article  Google Scholar 

  34. Matsumoto, T., and K. Hayashi. Mechanical and dimensional adaptation of rat aorta to hypertension. J. Biomech. Eng. 116(3):278–283, 1994.

    Article  Google Scholar 

  35. McKee, C. T., J. A. Last, P. Russell, and C. J. Murphy. Indentation versus tensile measurements of Young’s modulus for soft biological tissues. Tissue Eng. Part B Rev. 17(3):155–164, 2011.

    Article  Google Scholar 

  36. Murata, K., T. Motayama, and C. Kotake. Collagen types in various layers of the human aorta and their changes with the atherosclerotic process. Atherosclerosis 60(3):251–262, 1986.

    Article  Google Scholar 

  37. Ocallaghan, C. J., and B. Williams. Mechanical strain–induced extracellular matrix production by human vascular smooth muscle cells. Hypertension 36(3):319–324, 2000.

    Article  Google Scholar 

  38. O’Leary, S. A., J. J. Mulvihill, H. E. Barrett, E. G. Kavanagh, M. T. Walsh, T. M. McGloughlin, et al. Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue. J. Mech. Behav. Biomed. Mater. 42:154–167, 2015.

    Article  Google Scholar 

  39. Peloquin, J., J. Huynh, R. M. Williams, and C. A. Reinhart-King. Indentation measurements of the subendothelial matrix in bovine carotid arteries. J. Biomech. 44(5):815–821, 2011.

    Article  Google Scholar 

  40. Rezvani-Sharif, A., M. Tafazzoli-Shadpour, D. Kazemi-Saleh, and M. Sotoudeh-Anvari. Stress analysis of fracture of atherosclerotic plaques: crack propagation modeling. Med Biol Eng Comput. 55:1389–1400, 2016.

    Article  Google Scholar 

  41. Rho, J. Y., M. E. Roy, T. Y. Tsui, and G. M. Pharr. Elastic properties of microstructural components of human bone tissue as measured by nanoindentation. J. Biomed. Mater. Res. 45(1):48–54, 1999.

    Article  Google Scholar 

  42. Schiffrin, E. L., A. Tedgui, and S. Lehoux. mechanical stress and the arterial wall. Blood pressure and arterial wall mechanics in cardiovascular diseases. New York: Springer, pp. 97–106, 2014.

    Google Scholar 

  43. Stary, H. C., A. B. Chandler, R. E. Dinsmore, V. Fuster, S. Glagov, W. Insull, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis a report from the committee on vascular lesions of the council on arteriosclerosis. Am. Heart Assoc. Circ. 92(5):1355–1374, 1995.

    Google Scholar 

  44. Taghizadeh, H., M. Tafazzoli-Shadpour, and M. B. Shadmehr. Analysis of arterial wall remodeling in hypertension based on lamellar modeling. J. Am. Soc. Hypertens. 9(9):735–744, 2015.

    Article  Google Scholar 

  45. Taghizadeh, H., M. Tafazzoli-Shadpour, M. B. Shadmehr, and N. Fatouraee. Evaluation of biaxial mechanical properties of aortic media based on the lamellar microstructure. Materials 8(1):302–316, 2015.

    Article  Google Scholar 

  46. Taylor, C. A., T. J. Hughes, and C. K. Zarins. Finite element modeling of three-dimensional pulsatile flow in the abdominal aorta: relevance to atherosclerosis. Ann. Biomed. Eng. 26(6):975–987, 1998.

    Article  Google Scholar 

  47. Teng, Z., Y. Zhang, Y. Huang, J. Feng, J. Yuan, Q. Lu, et al. Material properties of components in human carotid atherosclerotic plaques: a uniaxial extension study. Acta Biomater. 10(12):5055–5063, 2014.

    Article  Google Scholar 

  48. Tracqui, P., A. Broisat, J. Toczek, N. Mesnier, J. Ohayon, and L. Riou. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy. J. Struct. Biol. 174(1):115–123, 2011.

    Article  Google Scholar 

  49. VanderBurgh, J. A., and C. A. Reinhart-King. The role of age-related intimal remodeling and stiffening in atherosclerosis. Adv. Pharmacol. 81:365–391, 2018.

    Article  Google Scholar 

  50. Vengrenyuk, Y., S. Carlier, S. Xanthos, L. Cardoso, P. Ganatos, R. Virmani, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc. Natl. Acad. Sci. 103(40):14678–14683, 2006.

    Article  Google Scholar 

  51. Wayman, B. H., W. R. Taylor, A. Rachev, and R. P. Vito. Arteries respond to independent control of circumferential and shear stress in organ culture. Ann. Biomed. Eng. 36(5):673–684, 2008.

    Article  Google Scholar 

  52. Wolinsky, H., and S. Glagov. A lamellar unit of aortic medial structure and function in mammals. Circ. Res. 20(1):99–111, 1967.

    Article  Google Scholar 

  53. Zieman, S. J., V. Melenovsky, and D. A. Kass. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler. Thromb. Vasc. Biol. 25(5):932–943, 2005.

    Article  Google Scholar 

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Acknowledgments

Authors thank Dr. Davood Kazemi-Saleh and Dr. Zahra Pourjafar at Baghiatallah Hospital for providing tissue specimens. Authors also thank Dr. Amirnader Emami Razavi at Tehran University of Medical Sciences for assistance in the preparation of samples for AFM test and determination of different components of atherosclerotic plaques and arterial wall layers in specimens.

Conflict of interest

Alireza Rezvani-Sharif, Mohammad Tafazzoli-Shadpour and Alberto Avolio declare that they have no conflict of interest.

Ethical Approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study. No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran

    Alireza Rezvani-Sharif & Mohammad Tafazzoli-Shadpour

  2. Department of Biomedical Science, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia

    Alireza Rezvani-Sharif & Alberto Avolio

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  1. Alireza Rezvani-Sharif
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  2. Mohammad Tafazzoli-Shadpour
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Correspondence to Mohammad Tafazzoli-Shadpour.

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Associate Editor Wei Sun and Ajit P. Yoganathan oversaw the review of this article.

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Rezvani-Sharif, A., Tafazzoli-Shadpour, M. & Avolio, A. Mechanical Characterization of the Lamellar Structure of Human Abdominal Aorta in the Development of Atherosclerosis: An Atomic Force Microscopy Study. Cardiovasc Eng Tech 10, 181–192 (2019). https://doi.org/10.1007/s13239-018-0370-1

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