Atherosclerosis
Volume 188, Issue 2 , Pages 221-230 , October 2006

Aging, smooth muscle cells and vascular pathobiology: Implications for atherosclerosis

  • Augusto Orlandi

      Affiliations

    • Anatomic Pathology Institute, Department of Biopathology, Tor Vergata University of Rome, Via Montpellier 1, Rome, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 06 20903960; fax: +39 06 20902209.
  • ,
  • Marie-Luce Bochaton-Piallat

      Affiliations

    • Department of Pathology and Immunology, University of Geneva, Switzerland
  • ,
  • Giulio Gabbiani

      Affiliations

    • Department of Pathology and Immunology, University of Geneva, Switzerland
  • ,
  • Luigi Giusto Spagnoli

      Affiliations

    • Anatomic Pathology Institute, Department of Biopathology, Tor Vergata University of Rome, Via Montpellier 1, Rome, Italy

Received 31 August 2005 ,Revised 10 January 2006 ,Accepted 18 January 2006.

References 

  1. Movat ZH, More MH, Haust MD. The diffuse intimal thickening of human aorta with aging. Am J Pathol. 1958;34:1023–1035
  2. Tracy RE, Strong JP, Toca VT, Lopez CR. Variable patterns of nonatheromatous aortic intimal thickening. Lab Invest. 1979;41:553–559
  3. Scebat L, Renais J, hadjisky P. Histometabolic and structural changes during arterial wall ageing. Possible role of immune process. In:  Cavallero C editors. The arterial wall in atherogenesis. Padova: Piccin, Medical Book; 1975;p. 43–60
  4. Orlandi A, Mauriello A, Marino B, Spagnoli LG. Age-related modifications of aorta and coronaries in the rabbit: a morphological and morphometrical assessment. Arch Gerontol Geriatr. 1993;17:37–53
  5. Virmani R, Avolio AP, Mergner WJ, et al. Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities. Am J Pathol. 1991;139:1119–1129
  6. Friedman MN. A biologically plausible model of thickening of arterial intima under shear. Arteriosclerosis. 1989;9:511–522
  7. Hoover GA, Nicolosi RJ, Camp RR, Hayes KC. Characteristics of the aortic intima in young and old cebus and squirrel monkeys. Arteriosclerosis. 1982;2:252–265
  8. Gerrity RG, Cliff WJ. The aortic tunica intima in young and aging rats. Exp Mol Pathol. 1972;16:382–402
  9. Wolinsky H. Long-term effects of hypertension on the rat aortic wall and their relation to concurrent aging changes. Morphological and chemical studies. Circ Res. 1972;30:301–309
  10. Mosse PR, Campbell GR, Campbell JH. Smooth muscle phenotypic expression in human carotid arteries. II. Atherosclerosis-free diffuse intimal thickenings compared with the media. Arteriosclerosis. 1986;6:664–669
  11. Takaichi S, Yutani C, Fujita H, Yamamoto A. Ultrastructural studies on the phenotypic modulation of human intimal smooth muscle cells. Atherosclerosis. 1993;100:197–211
  12. Orlandi A, Marcellini M, Spagnoli LG. Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 2000;20:1123–1136
  13. Faggiotto A, Ross R, Harker L. Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis. 1984;4:323–340
  14. Geer JC, Haust MD. Smooth muscle cells in atherosclerosis. Monogr Atheroscler. 1972;2:1–140
  15. Fornieri C, Quaglino D, Mori G. Role of the extracellular matrix in age-related modifications of the rat aorta. Ultrastructural, morphometric, and enzymatic evaluations. Arterioscler Thromb. 1992;12:1008–1016
  16. Li Z, Froehlich J, Galis ZS, Lakatta EG. Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats. Hypertension. 1999;33:116–123
  17. Jacob MP. Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother. 2003;57:195–202
  18. Cliff WJ. The aortic tunica media in aging rats. Exp Mol Pathol. 1970;13:172–189
  19. Spina M, Garbisa S, Hinnie J, et al. Age-related changes in composition and mechanical properties of the tunica media of the upper thoracic human aorta.. Arteriosclerosis. 1983;3:64–76
  20. Atkinson J. Aging of arterial extracellular matrix elastin: etiology and consequences. Pathol Biol (Paris). 1998;46:555–559
  21. Elliott RJ, McGrath LT. Calcification of the human thoracic aorta during aging. Calcif Tissue Int. 1994;54:268–273
  22. Nakamura T, Tokita K, Tateno S, et al. Human aortic acid mucopolysaccharides and glycoproteins. Changes during ageing and in atherosclerosis. J Atheroscler Res. 1968;8:891–902
  23. Wight TN, Ross R. Proteoglycans in primate arteries. I. Ultrastructural localization and distribution in the intima. J Cell Biol. 1975;67:660–674
  24. Kumar V, Berenson GS, Ruiz H, et al. Acid mucopolysaccharides of human aorta. 1. Variations with maturation. J Atheroscler Res. 1967;7:573–581
  25. Tracy RE. Medial thickenings of coronary artery and the aging risk factor for atherosclerosis. Atherosclerosis. 2001;155:337–346
  26. Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol. 1992;23:1–34
  27. Wautier JL, Schmidt AM. Protein glycation: a firm link to endothelial cell dysfunction. Circ Res. 2004;95:233–238
  28. Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest. 1997;99:457–468
  29. Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest. 1991;87:432–438
  30. Sakaguchi T, Yan SF, Yan SD, et al. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest. 2003;111:959–972
  31. Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res. 1999;84:489–497
  32. Bierman EL, Ross R. Aging and atherosclerosis. In:  Paoletti R,  Gotto AM editor. Atherosclerosis review. vol. 2:New York: Raven Press; 1977;p. 79
  33. McGill HC, Geer JC, Strong GP. In:  Sandler M,  Bourne J editor. Atherosclerosis and its origin. New York: Academic Press; 1963;p. 39–66
  34. Spagnoli LG, Mauriello A, Orlandi A, Sangiorgi G, Bonanno E. Age-related changes affecting atherosclerotic risk: potential for pharmacological intervention. Drugs Aging. 1996;8:275–298
  35. Luscher TF, Tanner FC, Dohi Y. Age, hypertension and hypercholesterolemia alter endothelium-dependent vascular regulation. Pharmacol Toxicol. 1992;70(suppl):32–39
  36. Stary HC. Macrophages, macrophage foam cells, and eccentric intimal thickening in the coronary arteries of young children. Atherosclerosis. 1987;64:91–108
  37. Woolf N. Morphological changes in atherosclerosis and the effects of hyperlipidemia on the artery wall. In:  Stokes J,  Mancini M editor. Atherosclerosis review. vol. 18:New York: Raven Press Ltd.; 1988;p. 25–48
  38. Barnes SE, Weinberg PD. Contrasting patterns of spontaneous aortic disease in young and old rabbits. Arterioscler Thromb Vasc Biol. 1998;18:300–308
  39. Spagnoli LG, Orlandi A, Mauriello A, et al. Aging and atherosclerosis in the rabbits, 1: distribution, prevalence and morphology of atherosclerotic lesions. Atherosclerosis. 1991;89:11–24
  40. Clarkson TB, Lofland HB, Bullock BC, et al. Atherosclerosis in some species of New World monkeys. Ann NY Acad Sci. 1969;162:103–109
  41. Bobik A, Campbell JH. Vascular derived growth factors: cell biology, pathophysiology, and pharmacology. Pharmacol Rev. 1993;45:1–42
  42. Spagnoli LG, Orlandi A, Bonaventura M, et al. Propionyl-l-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits. Atherosclerosis. 1995;114:29–44
  43. Rosenfeld ME, Ross R. Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1990;10:680–687
  44. Chajara A, Delpech B, Courel MN, et al. Effect of aging on neointima formation and hyaluronan, hyaluronidase and hyaluronectin production in injured rat aorta. Atherosclerosis. 1998;138:53–64
  45. Clowes AW, Reidy MA, Clowes MM. Mechanisms of stenosis after arterial injury. Lab Invest. 1983;49:208–215
  46. Forrester J. Intimal disruption and coronary thrombosis: its role in the pathogenesis of human coronary disease. Am J Cardiol. 1991;68:69B–77B
  47. Stemerman MB, Weinstein R, Rowe JW, et al. Vascular smooth muscle cell growth kinetics in vivo in aged rats. Proc Natl Acad Sci USA. 1982;79:3863–3866
  48. McCaffrey TA, Nicholson AC, Szabo PE, et al. Aging and arteriosclerosis. The increased proliferation of arterial smooth muscle cells isolated from old rats is associated with increased platelet-derived growth factor-like activity. J Exp Med. 1988;167:163–174
  49. Patek PR, Valentin A, de Mignard MD, Bernick S. Changes in structure of coronary arteries. Susceptibility to arteriosclerosis in old rats. Arch Pathol. 1968;85:388–397
  50. Stout RW, Bierman EL, Ross R. Effect of insulin on the proliferation of cultured primate arterial smooth muscle cells. Circ Res. 1975;36:319–327
  51. Bierman EL. The effect of donor age on the in vitro life span of cultured human arterial smooth-muscle cells. In Vitro. 1978;14:951–955
  52. Grunwald J, Mey J, Schonleben W, et al. Cultivated human arterial smooth muscle cells. The effect of donor age, blood pressure, diabetes and smoking on in vitro cell growth. Pathol Biol (Paris). 1983;31:819–823
  53. Spagnoli LG, Sambuy Y, Palmieri G, Mauriello A. Age-related modulation of vascular smooth muscle cells proliferation following arterial wall damage. Artery. 1985;13:187–198
  54. Hariri RJ, Alonso DR, Hajjar DP, et al. Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury. J Exp Med. 1986;164:1171–1178
  55. Hariri RJ, Hajjar DP, Coletti D, et al. Aging and arteriosclerosis. Cell cycle kinetics of young and old arterial smooth muscle cells. Am J Pathol. 1988;131:132–136
  56. Start RD, Loomes RS, Shortland JR. The relationship between donor age and the growth characteristics of human smooth muscle cultures of aorta and stomach. Int J Exp Pathol. 1991;72:647–654
  57. McCaffrey TA, Falcone DJ. Evidence for an age-related dysfunction in the antiproliferative response to transforming growth factor-beta in vascular smooth muscle cells. Mol Biol Cell. 1993;4:315–322
  58. Bochaton-Piallat ML, Gabbiani F, Ropraz P, Gabbiani G. Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones. Arterioscler Thromb Vasc Biol. 1993;13:1449–1455
  59. Porreca E, Di Febbo C, Pandolfi A, et al. Differences in the glutathione system of cultured aortic smooth muscle cells from young and aged rats. Atherosclerosis. 1993;100:141–148
  60. Li Z, Cheng H, Lederer WJ, et al. Enhanced proliferation and migration and altered cytoskeletal proteins in early passage smooth muscle cells from young and old rat aortic explants. Exp Mol Pathol. 1997;64:1–11
  61. Ruiz-Torres A, Gimeno A, Melon J, et al. Age-related loss of proliferative activity of human vascular smooth muscle cells in culture. Mech Ageing Dev. 1999;110:49–55
  62. Ruiz-Torres A, Lozano R, Melon J, Carraro R. Age-dependent decline of in vitro migration (basal and stimulated by IGF-1 or insulin) of human vascular smooth muscle cells. J Gerontol A Biol Sci Med Sci. 2003;58:B1074–B1077
  63. Arking R. Aging as an intracellular-based process. Biology of aging, observations and principles. New York: Prentice-Hall International; 1991;337–354
  64. Orlandi A, Ropraz P, Gabbiani G. Proliferative activity and alpha-smooth muscle actin expression in cultured rat aortic smooth muscle cells are differently modulated by transforming growth factor-beta 1 and heparin. Exp Cell Res. 1994;214:528–536
  65. Fenton M, Barker S, Kurz DJ, Erusalimsky JD. Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries. Arterioscler Thromb Vasc Biol. 2001;21:220–226
  66. Azuma H, Niimi Y, Terada T, Hamasaki H. Accelerated endothelial regeneration and intimal hyperplasia following a repeated denudation of rabbit carotid arteries: morphological and immunohistochemical studies. Clin Exp Pharmacol Physiol. 1995;22:748–754
  67. Han DKM, Haudenschild CC, Hong MK, et al. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol. 1995;147:267–277
  68. Bennet MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessel and coronary atherosclerotic plaque. J Clin Invest. 1995;95:2266–2274
  69. Bochaton-Piallat ML, Gabbiani F, Redard M, et al. Apoptosis participates in cellularity regulation during rat aortic intimal thickening. Am J Pathol. 1995;146:1059–1064
  70. Haunstetter A, Izumo S. Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ Res. 1998;82:1111–1129
  71. Urano Y, Shirai K, Watanabe H, et al. Vascular smooth muscle cell outgrowth, proliferation, and apoptosis in young and old rats. Atherosclerosis. 1999;146:101–105
  72. Pollman MJ, Hall JL, Gibbon GH. Determinants of vascular smooth muscle cell apoptosis after balloon angioplasty injury. Circ Res. 1996;84:113–121
  73. Moon SK, Thompson LJ, Madamanchi N, et al. Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells. Am J Physiol Heart Circ Physiol. 2001;280:H2779–H2788
  74. Walker LN, Bowen-Pope DF, et al. Production of platelet-derived growth factor-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury. Proc Natl Acad Sci USA. 1986;83:7311–7315
  75. Kocher O, Skalli O, Bloom WS, Gabbiani G. Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening. Lab Invest. 1984;50:645–652
  76. Seifert RA, Schwartz SM, Bowen-Pope DF. Developmentally regulated production of platelet-derived growth factor-like molecules. Nature. 1984;311:669–671
  77. Orlandi A, Francesconi A, Cocchia D, et al. Phenotypic heterogeneity influences apoptotic susceptibility to retinoic acid and cis-platinum of rat arterial smooth muscle cells in vitro: implications for the evolution of experimental intimal thickening. Arterioscler Thromb Vasc Biol. 2001;21:1118–1123
  78. Orlandi A, Ehrlich HP, Ropraz P, et al. Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro. Arterioscler Thromb. 1994;14:982–989
  79. Owens GK. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev. 1995;75:487–517
  80. Kuro-o M, Nagai R, Tsuchimochi H, et al. Developmentally regulated expression of vascular smooth muscle myosin heavy chain isoforms. J Biol Chem. 1989;264:18272–18275
  81. Nikkari ST, Koistinaho J, Jaakkola O. Changes in the composition of cytoskeletal and cytocontractile proteins of rat aortic smooth muscle cells during aging. Differentiation. 1990;44:216–221
  82. Cremona O, Muda M, Appel RD, et al. Differential protein expression in aortic smooth muscle cells cultured from newborn and aged rats. Exp Cell Res. 1995;217:280–287
  83. Bochaton-Piallat ML, Ropraz P, Gabbiani F, Gabbiani G. Phenotypic heterogeneity of rat arterial smooth muscle cell clones. Implications for the development of experimental intimal thickening. Arterioscler Thromb Vasc Biol. 1996;16:815–820
  84. Jones MR, Ravid K. Vascular smooth muscle polyploidization as a biomarker for aging and its impact on differential gene expression. J Biol Chem. 2004;279:5306–5313
  85. Bochaton-Piallat ML, Clowes AW, Clowes MM, et al. Cultured arterial smooth muscle cells maintain distinct phenotypes when implanted into carotid artery. Arterioscler Thromb Vasc Biol. 2001;21:949–954
  86. Luscher TF, Tanner FC, Dohi Y. Age, hypertension and hypercholesterolemia alter endothelium-dependent vascular regulation. Pharmacol Toxicol. 1992;70(suppl):32–39
  87. Yan ZQ, Sirsjo A, Bochaton-Piallat ML, Gabbiani G, Hansson GK. Augmented expression of inducible NO synthase in vascular smooth muscle cells during aging is associated with enhanced NF-kappaB activation. Arterioscler Thromb Vasc Biol. 1999;19:2854–2862
  88. Chan GH, Fiscus RR. Exaggerated production of nitric oxide (NO) and increases in inducible NO-synthase mRNA levels induced by the pro-inflammatory cytokine interleukin-1beta in vascular smooth muscle cells of elderly rats. Exp Gerontol. 2004;39:387–394
  89. Ferrini MG, Davila HH, Valente EG, et al. Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media. Cardiovasc Res. 2004;61:796–805
  90. Spinetti G, Wang M, Monticone R, et al. Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler Thromb Vasc Biol. 2004;24:1397–1402
  91. Eggena P, Morin AM, Barrett JD, Krall JF. The influence of aging on angiotensinogen production by rat vascular smooth muscle cells in vitro. Clin Exp Hypertens A. 1988;10:597–603
  92. Lundberg MS, Crow MT. Age-related changes in the signaling and function of vascular smooth muscle cells. Exp Gerontol. 1999;34:549–557
  93. Dohi Y, Kojima M, Sato K, Luscher TF. Age-related changes in vascular smooth muscle and endothelium. Drugs Aging. 1995;7:278–291
  94. Csiszar A, Ungvari Z, Edwards JG, et al. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res. 2002;90:1159–1166
  95. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809
  96. Saiura A, Sata M, Hirata Y, et al. Circulating smooth muscle progenitor cells contribute to atherosclerosis. Nat Med. 2001;7:382–383
  97. Shimizu K, Sugiyama S, Aikawa M, et al. Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy. Nat Med. 2001;7:738–741
  98. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004;84:767–801
  99. Miyamoto T, et al. Expression of stem cell factor in human aortic endothelial and smooth muscle cells. Atherosclerosis. 1997;129:207–213
  100. Skowasch D, Jabs A, Andrie R, et al. Presence of bone-marrow- and neural-crest-derived cells in intimal hyperplasia at the time of clinical in-stent restenosis. Cardiovasc Res. 2003;60:684–691
  101. Ahn Y, Jeong MH, Schwartz RS. Changing paradigm for neointimal cell origin: is restenosis a blood-borne disease?. Catheter Cardiovasc Interv. 2005;64:468–470
  102. Libby P. Bone marrow: a fountain of vascular youth?. Circulation. 2003;108:378–379
  103. Stary HC, Blankenhorn DH, Chandler , et al. A definition of the intima of human arteries and of its atherosclerosis-prone regions. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1992;85:391–405
  104. Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, et al. Aging, progenitor cell exhaustion, and atherosclerosis. Circulation. 2003;108:457–463

PII: S0021-9150(06)00043-8

doi: 10.1016/j.atherosclerosis.2006.01.018

Atherosclerosis
Volume 188, Issue 2 , Pages 221-230 , October 2006