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Loss of elastic fiber integrity compromises common carotid artery function: Implications for vascular aging

Abstract

Competent elastic fibers endow central arteries with the compliance and resilience that are fundamental to their primary mechanical function in vertebrates. That is, by enabling elastic energy to be stored in the arterial wall during systole and then to be used to work on the blood during diastole, elastic fibers decrease ventricular workload and augment blood flow in pulsatile systems. Indeed, because elastic fibers are formed during development and stretched during somatic growth, their continual tendency to recoil contributes to the undulation of the stiffer collagen fibers, which facilitates further the overall compliance of the wall under physiologic pressures while allowing the collagen to limit over-distension during acute increases in blood pressure. In this paper, we use consistent methods of measurement and quantification to compare the biaxial material stiffness, structural stiffness, and energy storage capacity of murine common carotid arteries having graded degrees of elastic fiber integrity – normal, elastin-deficient, fibrillin-1 deficient, fibulin-5 null, and elastase-treated. The finding that the intrinsic material stiffness tends to be maintained nearly constant suggests that intramural cells seek to maintain a favorable micromechanical environment in which to function. Nevertheless, a loss of elastic energy storage capability due to the loss of elastic fiber integrity severely compromises the primary function of these central arteries.

References

  1. Clark JM, Glagov S. Transmural organization of the arterial media. The lamellar unit revisited. Arterioscler Thromb Vasc Biol 1985;5(1):19–34.

    Google Scholar 

  2. Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev 2009;89(3):957–89.

    Google Scholar 

  3. Davis EC. Stability of Elastin in the developing mouse Aorta: a quantitative radioautographic study. Histochemistry 1993; 100(1):17–26.

    Google Scholar 

  4. Davis EC. Elastic lamina growth in the developing mouse aorta. J Histochem Cytochem 1995;43(11):1115–23.

    Google Scholar 

  5. Arribas SM, Hinek A, González MC. Elastic fibres and vascular structure in hypertension. Pharmacol Ther 2006;111(3):771–91.

    Google Scholar 

  6. Sherratt MJ. Tissue elasticity and the ageing elastic fibre. AGE 2009;31(4):305–25.

    Google Scholar 

  7. Lillie MA, Gosline JM. Limits to the durability of arterial elastic tissue. Biomaterials 2007;28(11):2021–31.

    Google Scholar 

  8. O’Rourke MF, Hashimoto J. Mechanical factors in arterial aging: a clinical perspective. J Am Coll Cardiol 2007;50(1):1–13.

    Google Scholar 

  9. Hornebeck W, Emonard H. The cell-elastin-elastase(s) interacting triade directs elastolysis. Front Biosci Landmark Ed 2011;16:707–22.

    Google Scholar 

  10. Lakatta EG, Wang M, Najjar SS. Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. Med Clin North Am 2009;93(3):583–604.

    Google Scholar 

  11. Lacolley P, Challande P, Osborne-Pellegrin M, Regnault V. Genetics and pathophysiology of arterial stiffness. Cardiovasc Res 2009;81(4):637–48.

    Google Scholar 

  12. Safar ME. Arterial aging – hemodynamic changes and therapeutic options. Nat Rev Cardiol 2010;7(8):442–9.

    Google Scholar 

  13. Pratt B, Curci J. Arterial elastic fiber structure. Function and potential roles in acute aortic dissection. J Cardiovasc Surg (Torino) 2010;51(5):647–56.

    Google Scholar 

  14. Wilson JS, Baek S, Humphrey JD. Importance of initial aortic properties on the evolving regional anisotropy, stiffness and wall thickness of human abdominal aortic aneurysms. J R Soc Interface 2012;9(74):2047–58.

    Google Scholar 

  15. Maurice P, Blaise S, Gayral S, Debelle L, Laffargue M, Hornebeck W, et al. Elastin fragmentation and atherosclerosis progression: the elastokine concept. Trends cardiovasc Med 2013;23(6):211–21.

    Google Scholar 

  16. Kielty CM. Elastic fibres in health and disease. Expert Rev Mol Med 2006;8(19):1–23.

    Google Scholar 

  17. Ramirez F, Dietz HC. Fibrillin-rich microfibrils: structural determinants of morphogenetic and homeostatic events. J Cell Physiol 2007;213(2):326–30.

    Google Scholar 

  18. Yanagisawa H, Davis EC. Unraveling the mechanism of elastic fiber assembly: the roles of short fibulins. Int J Biochem Cell Biol 2010;42(7):1084–93.

    Google Scholar 

  19. Faury G. Function–structure relationship of elastic arteries in evolution: from microfibrils to elastin and elastic fibres. Pathol Biol 2001;49(4):310–25.

    Google Scholar 

  20. Ferruzzi J, Collins MJ, Yeh AT, Humphrey JD. Mechanical assessment of elastin integrity in fibrillin-1-deficient carotid arteries: implications for Marfan syndrome. Cardiovasc Res 2011;92(2):287–95.

    Google Scholar 

  21. Karnik SK, Brooke BS, Bayes-Genis A, Sorensen L, Wythe JD, Schwartz RS, et al. A critical role for elastin signaling in vascular morphogenesis and disease. Development 2003; 130(2):411–23.

    Google Scholar 

  22. Michel J-B. Anoïkis in the cardiovascular system known and unknown extracellular mediators. Arterioscler Thromb Vasc Biol 2003;23(12):2146–54.

    Google Scholar 

  23. Ferruzzi J, Bersi MR, Humphrey JD. Biomechanical phenotyping of central arteries in health and disease: advantages of and methods for murine models. Ann Biomed Eng 2013;41(7): 1311–30.

    Google Scholar 

  24. Ferruzzi J, Bersi MR, Uman S, Yanagisawa H, Humphrey JD. Decreased elastic energy storage, not increased material stiffness, characterizes central artery dysfunction in fibulin-5 deficiency independent of sex. J Biomech Eng 2015;137(3): 031007.

  25. Gleason RL, Wilson E, Humphrey JD, Gray SP. A multiaxial computer-controlled organ culture and biomechanical device for mouse carotid arteries. J Biomech Eng 2005;126(6): 787–95.

    Google Scholar 

  26. Humphrey JD, Eberth JF, Dye WW, Gleason RL. Fundamental role of axial stress in compensatory adaptations by arteries. J Biomech 2009;42(1):1–8.

    Google Scholar 

  27. Bersi MR, Ferruzzi J, Eberth JF, Gleason Jr RL, Humphrey JD. Consistent biomechanical phenotyping of common carotid arteries from seven genetic, pharmacological, and surgical mouse models. Ann Biomed Eng 2014;42(6):1207–23.

    Google Scholar 

  28. Gleason RL, Dye WW, Wilson E, Humphrey JD. Quantification of the mechanical behavior of carotid arteries from wild-type, dystrophin-deficient, and sarcoglycan-δ knockout mice. J Biomech 2008;41(15):3213–8.

    Google Scholar 

  29. Eberth JF, Taucer AI, Wilson E, Humphrey JD. Mechanics of carotid arteries in a mouse model of Marfan syndrome. Ann Biomed Eng 2009;37(6):1093–104.

    Google Scholar 

  30. Wan W, Yanagisawa H, Gleason Jr RL. Biomechanical and microstructural properties of common carotid arteries from fibulin-5 null mice. Ann Biomed Eng 2010;38(12):3605–17.

    Google Scholar 

  31. Van Loon P. Length-force and volume-pressure relationships of arteries. Biorheology 1977;14(4):181–201.

    Google Scholar 

  32. Weizsäcker HW, Lambert H, Pascale K. Analysis of the passive mechanical properties of rat carotid arteries. J Biomech 1983; 16(9):703–15.

    Google Scholar 

  33. Wagenseil JE, Mecham RP. Elastin in large artery stiffness and hypertension, J. Cardiovasc Transl Res 2012;5(3):264–73.

    Google Scholar 

  34. Fung YC. Elasticity of soft tissues in simple elongation. Am J Physiol – Leg Content 1967;213(6):1532–44.

    Google Scholar 

  35. Yanagisawa H, Davis EC, Starcher BC, Ouchi T, Yanagisawa M, Richardson JA, et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 2002; 415(6868):168–71.

    Google Scholar 

  36. Nakamura T, Lozano PR, Ikeda Y, Iwanaga Y, Hinek A, Minamisawa S, et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 2002;415(6868):171–5.

    Google Scholar 

  37. Benetos A, Laurent S, Hoeks AP, Boutouyrie PH, Safar ME. Arterial alterations with aging and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler Thromb Vasc Biol 1993;13(1):90–7.

    Google Scholar 

  38. Laurent S, Katsahian S, Fassot C, Tropeano A-I, Gautier I, Laloux B, et al. Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke 2003;34(5): 1203–6.

    Google Scholar 

  39. Dietz HC, Mecham RP. Mouse models of genetic diseases resulting from mutations in elastic fiber proteins. Matrix Biol 2000;19(6):481–8.

    Google Scholar 

  40. Marque V, Kieffer P, Gayraud B, Lartaud-Idjouadiene I, Ramirez F, Atkinson J. Aortic wall mechanics and composition in a transgenic mouse model of marfan syndrome. Arterioscler Thromb Vasc Biol 2001;21(7):1184–9.

    Google Scholar 

  41. Faury G, Pezet M, Knutsen RH, Boyle WA, Heximer SP, McLean SE, et al. Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. J Clin Invest 2003;112(9):1419–28.

    Google Scholar 

  42. Wagenseil JE, Nerurkar NL, Knutsen RH, Okamoto RJ, Li DY, Mecham RP. Effects of elastin haploinsufficiency on the mechanical behavior of mouse arteries. Am J Physiol – Heart Circ Physiol 2005;289(3):H1209–17.

    Google Scholar 

  43. Chung AWY, Yeung KA, Sandor GGS, Judge DP, Dietz HC, Breemen C van. Loss of elastic fiber integrity and reduction of vascular smooth muscle contraction resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in the thoracic aortic aneurysm in Marfan syndrome. Circ Res 2007; 101(5):512–22.

    Google Scholar 

  44. Pezet M, Jacob M-P, Escoubet B, Gheduzzi D, Tillet E, Perret P, et al. Elastin haploinsufficiency induces alternative aging processes in the aorta. Rejuvenation Res 2008;11(1):97–112.

    Google Scholar 

  45. Carta L, Wagenseil JE, Knutsen RH, Mariko B, Faury G, Davis EC, et al. Discrete contributions of elastic fiber components to arterial development and mechanical compliance. Arterioscler Thromb Vasc Biol 2009;29(12):2083–9.

    Google Scholar 

  46. Haskett D, Doyle JJ, Gard C, Chen H, Ball C, Estabrook MA, et al. Altered tissue behavior of a non-aneurysmal descending thoracic aorta in the mouse model of Marfan syndrome. Cell Tissue Res 2011;347(1):267–77.

    Google Scholar 

  47. Le VP, Knutsen RH, Mecham RP, Wagenseil JE. Decreased aortic diameter and compliance precedes blood pressure increases in postnatal development of elastin-insufficient mice. Am J Physiol – Heart Circ Physiol 2011;301(1):H221–9.

    Google Scholar 

  48. Mariko B, Pezet M, Escoubet B, Bouillot S, Andrieu J-P, Starcher B, et al. Fibrillin-1 genetic deficiency leads to pathological ageing of arteries in mice. J Pathol 2011;224(1): 33–44.

    Google Scholar 

  49. Wan W, Gleason RL. Dysfunction in elastic fiber formation in fibulin-5 null mice abrogates the evolution in mechanical response of carotid arteries during maturation. Am J Physiol – Heart Circ Physiol 2013;304(5):H674–86.

    Google Scholar 

  50. Atabek HB. Wave propagation through a viscous fluid contained in a tethered, initially stressed, orthotropic elastic tube. Biophys J 1968;8(5):626–49.

    Google Scholar 

  51. Demiray H. Wave propagation through a viscous fluid contained in a prestressed thin elastic tube. Int J Eng Sci 1992;30(11): 1607–20.

    Google Scholar 

  52. Schwill S, Seppelt P, Gruünhagen J, Ott C-E, Jugold M, Ruhparwar A, et al. The fibrillin-1 hypomorphic mgR/mgR murine model of Marfan syndrome shows severe elastolysis in all segments of the aorta. J Vasc Surg 2013;57(6). 1628–1636.e3.

    Google Scholar 

  53. Le VP, Stoka KV, Yanagisawa H, Wagenseil JE. Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation. Physiol Rep 2014;2(3):e00257.

    Google Scholar 

  54. Avolio A. Ageing and wave reflection. J Hypertens 1992;10(6): S83–6.

    Google Scholar 

  55. Wagenseil JE, Knutsen RH, Li DY, Mecham RP. Elastin-Insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture. Am J Physiol – Heart Circ Physiol 2007;293(1):H574–82.

    Google Scholar 

  56. Adji A, O’Rourke MF, Namasivayam M. Arterial stiffness, its assessment, prognostic value, and implications for treatment. Am J Hypertens 2011;24(1):5–17.

    Google Scholar 

  57. Barodka VM, Joshi BL, Berkowitz DE, Hogue CW, Nyhan D. Implications of vascular aging. Anesth Analg 2011;112(5): 1048–60.

    Google Scholar 

  58. Kozel BA, Knutsen RH, Ye L, Ciliberto CH, Broekelmann TJ, Mecham RP. Genetic modifiers of cardiovascular phenotype caused by elastin haploinsufficiency act by extrinsic non-complementation. J Biol Chem 2011;286(52):44926–36.

    Google Scholar 

  59. Osei-Owusu P, Knutsen RH, Kozel BA, Dietrich HH, Blumer KJ, Mecham RP. Altered reactivity of resistance vasculature contributes to hypertension in elastin insufficiency. Am J Physiol – Heart Circ Physiol 2014;306(5):H654–66.

    Google Scholar 

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

    Google Scholar 

  61. Shadwick RE. Mechanical design in arteries. J Exp Biol 1999; 202(23):3305–13.

    Google Scholar 

  62. Humphrey JD, Dufresne ER, Schwartz MA. Mechanotransduction and extracellular matrix homeostasis. Nat Rev Mol Cell Biol 2014;15(12):802–12.

    Google Scholar 

  63. Humphrey JD. Cardiovascular solid mechanics: cells, tissues, and organs. New York: Springer; 2002.

    Google Scholar 

  64. Baek S, Gleason RL, Rajagopal KR, Humphrey JD. Theory of small on large: potential utility in computations of fluid–solid interactions in arteries. Comput Methods Appl Mech Eng 2007; 196(31–32):3070–8.

    Google Scholar 

  65. Taylor JR. An introduction to error analysis: the study of uncertainties in physical measurements. Sausalito, Calif: University Science Books; 1997.

    Google Scholar 

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Correspondence to J. D. Humphrey.

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Ferruzzi, J., Bersi, M.R., Mecham, R.P. et al. Loss of elastic fiber integrity compromises common carotid artery function: Implications for vascular aging. Artery Res 14, 41–52 (2016). https://doi.org/10.1016/j.artres.2016.04.001

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