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Smooth muscle cell differentiation: Mechanisms and models for vascular diseases

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  • Published:
Frontiers in Biology

Abstract

Background

Vascular smooth muscle cells (VSMCs) are mature cells that play critical roles in both normal and aberrant cardiovascular conditions. In response to various environmental cues, VSMCs can dedifferentiate from a contractile state to a highly proliferative synthetic state through the so-called ‘phenotypic switching’ process. Changes in VSMC phenotype contribute to numerous vascular-related diseases, including atherosclerosis, calcification, and restenosis following angioplasty. Adventitial VSMC progenitor cells also contribute to formation of the neointima.

Methods/Results

Herein, we review both, the roles of VSMC differentiation in vascular diseases, and the in vitro models used to investigate the molecular mechanisms involved in the regulation of VSMC differentiation and phenotype modulation.

Conclusion

A comprehensive understanding of VSMC behavior in vascular diseases is essential to identify new therapeutic targets for the prevention and treatment of cardiovascular diseases.

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References

  1. Abedin M, Tintut Y, Demer L L (2004). Mesenchymal stem cells and the artery wall. Circ Res, 95(7): 671–676

    Article  CAS  PubMed  Google Scholar 

  2. Ackers-Johnson M, Talasila A, Sage A P, Long X, Bot I, Morrell N W, Bennett M R, Miano J M, Sinha S (2015). Myocardin regulates vascular smooth muscle cell inflammatory activation and disease. Arterioscler Thromb Vasc Biol, 35(4): 817–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aicher A, Zeiher AM, Dimmeler S (2005). Mobilizing endothelial progenitor cells. Hypertension (Dallas, Tex: 1979), 45(3): 321–325

    Article  CAS  Google Scholar 

  4. Ailawadi G, Eliason J L, Upchurch G R Jr (2003). Current concepts in the pathogenesis of abdominal aortic aneurysm. J Vasc Surg, 38(3): 584–588

    Article  PubMed  Google Scholar 

  5. Ailawadi G, Moehle C W, Pei H, Walton S P, Yang Z, Kron I L, Lau C L, Owens G K (2009). Smooth muscle phenotypic modulation is an early event in aortic aneurysms. J Thorac Cardiovasc Surg, 138(6): 1392–1399

    Article  PubMed  PubMed Central  Google Scholar 

  6. Airhart N, Brownstein B H, Cobb J P, Schierding W, Arif B, Ennis T L, Thompson R W, Curci J A (2014). Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin. J Vasc Surg, 60(4): 1033–1041, discussion 1041–1042

    Article  PubMed  Google Scholar 

  7. Alexander M R, Owens G K (2012). Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease. Annu Rev Physiol, 74(1): 13–40

    Article  CAS  PubMed  Google Scholar 

  8. Allahverdian S, Chehroudi A C, McManus B M, Abraham T, Francis G A (2014). Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation, 129(15): 1551–1559

    Article  CAS  PubMed  Google Scholar 

  9. Baumgartner H R, Studer Ab(1963). Controlled over-dilatation of the abdominal aorta in normo- and hypercholesteremic rabbits. Pathol Microbiol, 26: 129–148

    CAS  Google Scholar 

  10. Baxter B T, Terrin MC, Dalman R L (2008). Medical management of small abdominal aortic aneurysms. Circulation, 117(14): 1883–1889

    Article  PubMed  PubMed Central  Google Scholar 

  11. Beamish J A, He P, Kottke-Marchant K, Marchant R E (2010). Molecular regulation of contractile smooth muscle cell phenotype: implications for vascular tissue engineering. Tissue Eng Part B Rev, 16(5): 467–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bennett M R, Sinha S, Owens G K (2016). Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res, 118(4): 692–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bessueille L, Magne D (2015). Inflammation: a culprit for vascular calcification in atherosclerosis and diabetes. Cell Mol Life Sci, 72 (13): 2475–2489

    Article  CAS  PubMed  Google Scholar 

  14. Blank R S, Swartz E A, Thompson M M, Olson E N, Owens G K (1995). A retinoic acid-induced clonal cell line derived from multipotential P19 embryonal carcinoma cells expresses smooth muscle characteristics. Circ Res, 76(5): 742–749

    Article  CAS  PubMed  Google Scholar 

  15. Boström K I, Rajamannan N M, Towler D A (2011). The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res, 109(5): 564–577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Boyd N L, Robbins K R, Dhara S K, West F D, Stice S L (2009). Human embryonic stem cell-derived mesoderm-like epithelium transitions to mesenchymal progenitor cells. Tissue Eng Part A, 15 (8): 1897–1907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Butoi E, Gan A M, Tucureanu M M, Stan D, Macarie R D, Constantinescu C, Calin M, Simionescu M, Manduteanu I (2016). Cross-talk between macrophages and smooth muscle cells impairs collagen and metalloprotease synthesis and promotes angiogenesis. Biochim Biophys Acta, 1863(7 7 Pt A): 1568–1578

    Article  CAS  PubMed  Google Scholar 

  18. Byon C H, Javed A, Dai Q, Kappes J C, Clemens T L, Darley-Usmar V M, McDonald J M, Chen Y (2008). Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem, 283(22): 15319–15327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Campagnolo P, Cesselli D, Al Haj Zen A, Beltrami A P, Kränkel N, Katare R, Angelini G, Emanueli C, Madeddu P (2010). Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential. Circulation, 121(15): 1735–1745

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chen N X, Duan D, O’Neill K D, Wolisi G O, Koczman J J, Laclair R, Moe S M (2006). The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells. Kidney Int, 70(6): 1046–1053

    Article  CAS  PubMed  Google Scholar 

  21. Chen S, Lechleider R J (2004). Transforming growth factor-betainduced differentiation of smooth muscle from a neural crest stem cell line. Circ Res, 94(9): 1195–1202

    Article  CAS  PubMed  Google Scholar 

  22. Clowes AW, Reidy MA, Clowes MM(1983). Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest, 49(3): 327–333

    CAS  PubMed  Google Scholar 

  23. Dahia P L (2000). PTEN, a unique tumor suppressor gene. Endocr Relat Cancer, 7(2): 115–129

    Article  CAS  PubMed  Google Scholar 

  24. Doyle A J, Redmond E M, Gillespie D L, Knight P A, Cullen J P, Cahill P A, Morrow D J (2015). Differential expression of Hedgehog/Notch and transforming growth factor-β in human abdominal aortic aneurysms. J Vasc Surg, 62(2): 464–470

    Article  PubMed  Google Scholar 

  25. Du F, Zhou J, Gong R, Huang X, Pansuria M, Virtue A, Li X, Wang H, Yang X F (2012). Endothelial progenitor cells in atherosclerosis. Front Biosci, 17: 2327–2349

    Article  CAS  PubMed Central  Google Scholar 

  26. Durgin B G, Cherepanova O A, Gomez D, Karaoli T, Alencar G F, Butcher J T, Zhou Y Q, Bendeck M P, Isakson B E, Owens G K, Connelly J J (2017). Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions. Am J Physiol Heart Circ Physiol, 312(5): H943–H958

    Article  PubMed  PubMed Central  Google Scholar 

  27. Feil S, Fehrenbacher B, Lukowski R, Essmann F, Schulze-Osthoff K, Schaller M, Feil R (2014). Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res, 115(7): 662–667

    Article  CAS  PubMed  Google Scholar 

  28. Fukui D, Miyagawa S, Soeda J, Tanaka K, Urayama H, Kawasaki S (2003). Overexpression of transforming growth factor beta1 in smooth muscle cells of human abdominal aortic aneurysm. Eur J Vasc Endovasc Surg, 25(6): 540–545

    Article  CAS  PubMed  Google Scholar 

  29. Fukumoto Y, Deguchi J O, Libby P, Rabkin-Aikawa E, Sakata Y, Chin M T, Hill C C, Lawler P R, Varo N, Schoen F J, Krane S M, Aikawa M (2004). Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques. Circulation, 110(14): 1953–1959

    Article  CAS  PubMed  Google Scholar 

  30. Furgeson S B, Simpson P A, Park I, Vanputten V, Horita H, Kontos C D, Nemenoff R A, Weiser-Evans MC (2010). Inactivation of thetumour suppressor, PTEN, in smooth muscle promotes a proinflammatory phenotype and enhances neointima formation. Cardiovasc Res, 86(2): 274–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gao F, Chambon P, Offermanns S, Tellides G, Kong W, Zhang X, Li W (2014). Disruption of TGF-β signaling in smooth muscle cell prevents elastase-induced abdominal aortic aneurysm. Biochem Biophys Res Commun, 454(1): 137–143

    Article  CAS  PubMed  Google Scholar 

  32. Owens G K, Kumar M S, Wamhoff B R (2004). Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev, 84(3): 767

    Article  CAS  PubMed  Google Scholar 

  33. Glass C K, Witztum J L (2001). Atherosclerosis. the road ahead. Cell, 104(4): 503–516

    Article  CAS  PubMed  Google Scholar 

  34. Guo X, Stice S L, Boyd N L, Chen S Y (2013). A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells. Am J Physiol Cell Physiol, 304(4): C289–C298

    Article  CAS  PubMed  Google Scholar 

  35. Ha J M, Yun S J, Jin S Y, Lee H S, Kim S J, Shin H K, Bae S S (2017). Regulation of vascular smooth muscle phenotype by crossregulation of krüppel-like factors. Korean J Physiol Pharmacol, 21 (1): 37–44

    Article  CAS  PubMed  Google Scholar 

  36. Ha J M, Yun S J, Kim YW, Jin S Y, Lee H S, Song S H, Shin H K, Bae S S (2015). Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1. Biochem Biophys Res Commun, 464(1): 57–62

    Article  CAS  PubMed  Google Scholar 

  37. Hayashi K, Shibata K, Morita T, Iwasaki K, Watanabe M, Sobue K (2004). Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor- I signaling in vascular smooth muscle cells. J Biol Chem, 279(39): 40807–40818

    Article  CAS  PubMed  Google Scholar 

  38. Hirschi K K, Majesky M W (2004). Smooth muscle stem cells. Anat Rec A Discov Mol Cell Evol Biol, 276(1): 22–33

    Article  PubMed  Google Scholar 

  39. Hirschi K K, Rohovsky S A, D’Amore P A (1998). PDGF, TGFbeta, and heterotypic cell-cell interactions mediate endothelial cellinduced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol, 141(3): 805–814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Holifield B, Helgason T, Jemelka S, Taylor A, Navran S, Allen J, Seidel C (1996). Differentiated vascular myocytes: are they involved in neointimal formation? J Clin Invest, 97(3): 814–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Horita H, Wysoczynski C L, Walker L A, Moulton KS, Li M, Ostriker A, Tucker R, McKinsey T A, Churchill M E, Nemenoff R A, Weiser-Evans M C (2016). Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation. Nat Commun,7: 10830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hu Y, Xu Q (2011). Adventitial biology: differentiation and function. Arterioscler Thromb Vasc Biol, 31(7): 1523–1529

    Article  CAS  PubMed  Google Scholar 

  43. Hu Y, Zhang Z, Torsney E, Afzal A R, Davison F, Metzler B, Xu Q (2004). Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice. J Clin Invest, 113(9): 1258–1265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Huang H, Zhao X, Chen L, Xu C, Yao X, Lu Y, Dai L, Zhang M (2006). Differentiation of human embryonic stem cells into smooth muscle cells in adherent monolayer culture. Biochem Biophys Res Commun, 351(2): 321–327

    Article  CAS  PubMed  Google Scholar 

  45. Jain M K, Layne M D, Watanabe M, Chin M T, Feinberg M W, Sibinga N E, Hsieh CM, Yet S F, Stemple D L, Lee ME (1998). In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells. J Biol Chem, 273(11): 5993–5996

    Article  CAS  PubMed  Google Scholar 

  46. Kim S H, Yun S J, Kim Y H, Ha J M, Jin S Y, Lee H S, Kim S J, Shin H K, Chung S W, Bae S S (2015). Essential role of krüppellike factor 5 during tumor necrosis factor α-induced phenotypic conversion of vascular smooth muscle cells. Biochem Biophys Res Commun, 463(4): 1323–1327

    Article  CAS  PubMed  Google Scholar 

  47. Kovacic J C, Boehm M (2009). Resident vascular progenitor cells: an emerging role for non-terminally differentiated vessel-resident cells in vascular biology. Stem Cell Res (Amst), 2(1): 2–15

    Article  Google Scholar 

  48. Koyama H, Raines E W, Bornfeldt K E, Roberts J M, and Ross R (1996). Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Cell, 87:1069–1078

    Article  CAS  PubMed  Google Scholar 

  49. Kramann R, Goettsch C, Wongboonsin J, Iwata H, Schneider R K, Kuppe C, Kaesler N, Chang-Panesso M, Machado F G, Gratwohl S, Madhurima K, Hutcheson J D, Jain S, Aikawa E, Humphreys B D (2016). Adventitial MSC-like cells are progenitors of vascular smooth muscle cells and drive vascular calcification in chronic kidney disease. Cell Stem Cell, 19(5): 628–642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lacolley P, Regnault V, Nicoletti A, Li Z, Michel J B (2012). The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles. Cardiovasc Res, 95(2): 194–204

    Article  CAS  PubMed  Google Scholar 

  51. Legein B, Temmerman L, Biessen E A, Lutgens E (2013). Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci, 70(20): 3847–3869

    Article  CAS  PubMed  Google Scholar 

  52. Li D Y, Brooke B, Davis E C, Mecham R P, Sorensen L K, Boak B B, Eichwald E, Keating M T (1998). Elastin is an essential determinant of arterial morphogenesis. Nature, 393(6682): 276–280

    Article  CAS  PubMed  Google Scholar 

  53. Li G, Chen S J, Oparil S, Chen Y F, Thompson J A (2000). Direct in vivo evidence demonstrating neointimal migration of adventitial fibroblasts after balloon injury of rat carotid arteries. Circulation, 101(12): 1362–1365

    Article  CAS  PubMed  Google Scholar 

  54. Li M, Izpisua Belmonte J C (2016). Mending a faltering heart. Circ Res, 118(2): 344–351

    Article  CAS  PubMed  Google Scholar 

  55. Li N, Cheng W, Huang T, Yuan J, Wang X, Song M (2015). Vascular adventitia calcification and its underlying mechanism. PLoS One, 10(7): e0132506

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Li W, Li Q, Jiao Y, Qin L, Ali R, Zhou J, Ferruzzi J, Kim R W, Geirsson A, Dietz H C, Offermanns S, Humphrey J D, Tellides G (2014). Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis. J Clin Invest, 124(2): 755–767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Libby P, Ridker P M, Hansson G K (2011). Progress and challenges in translating the biology of atherosclerosis. Nature, 473 (7347): 317–325

    Article  CAS  PubMed  Google Scholar 

  58. Liu G H, Barkho B Z, Ruiz S, Diep D, Qu J, Yang S L, Panopoulos A D, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung H L, Sancho-Martinez I, Zhang K, Yates J, Izpisua Belmonte J C (2011). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature, 472(7342): 221–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Liu T M, Lee E H (2013). Transcriptional regulatory cascades in Runx2-dependent bone development. Tissue Eng Part B Rev, 19 (3): 254–263

    Article  PubMed  CAS  Google Scholar 

  60. Majesky M W (2007). Developmental basis of vascular smooth muscle diversity. Arterioscler Thromb Vasc Biol, 27(6): 1248–1258

    Article  CAS  PubMed  Google Scholar 

  61. Majesky MW, Dong X R, Hoglund V, Mahoney WM Jr, Daum G (2011a). The adventitia: a dynamic interface containing resident progenitor cells. Arterioscler Thromb Vasc Biol, 31(7): 1530–1539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Majesky M W, Dong X R, Regan J N, Hoglund V J (2011b). Vascular smooth muscle progenitor cells: building and repairing blood vessels. Circ Res, 108(3): 365–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Majesky M W, Horita H, Ostriker A, Lu S, Regan J N, Bagchi A, Dong X R, Poczobutt J, Nemenoff R A,Weiser-EvansMC (2017). Differentiated smooth muscle cells generate a subpopulation of resident vascular progenitor cells in the adventitia regulated by Klf4. Circ Res, 120(2): 296–311

    Article  CAS  PubMed  Google Scholar 

  64. Manabe I, Owens G K (2001). Recruitment of serum response factor and hyperacetylation of histones at smooth muscle-specific regulatory regions during differentiation of a novel P19-derived in vitro smooth muscle differentiation system. Circ Res, 88(11): 1127–1134

    Article  CAS  PubMed  Google Scholar 

  65. Martinez-Moreno JM, Herencia C, Montes de Oca A, Diaz-Tocados JM, Vergara N, Gomez MJ, Lopez-Arguello SD, Camargo A, Peralbo-Santaella E, Rodriguez-Ortiz ME, Canalejo A, Rodríguez M, Muñoz-Castañeda J R, Almadén Y (2017). High phosphate induces a pro-inflammatory response by vascular smooth muscle cells. Modulation by vitamin D derivatives. Clin Sci (Lond), 131(13):1449–1463

    Article  CAS  Google Scholar 

  66. Marx S O, Totary-Jain H, Marks A R (2011). Vascular smooth muscle cell proliferation in restenosis. Circ Cardiovasc Interv, 4(1): 104–111

    Article  CAS  PubMed  Google Scholar 

  67. Mason D P, Kenagy R D, Hasenstab D, Bowen-Pope D F, Seifert R A, Coats S, Hawkins S M, Clowes A W (1999). Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery. Circ Res, 85(12): 1179–1185

    Article  CAS  PubMed  Google Scholar 

  68. Maurer J, Fuchs S, Jager R, Kurz B, Sommer L, Schorle H (2007). Establishment and controlled differentiation of neural crest stem cell lines using conditional transgenesis. Differentiation, 75(7): 580–591

    Article  CAS  PubMed  Google Scholar 

  69. McBurney MW (1993). P19 embryonal carcinoma cells. Int J Dev Biol, 37(1): 135–140

    CAS  PubMed  Google Scholar 

  70. McBurney M W, Rogers B J (1982). Isolation of male embryonal carcinoma cells and their chromosome replication patterns. Dev Biol, 89(2): 503–508

    Article  CAS  PubMed  Google Scholar 

  71. McCarty M F, DiNicolantonio J J (2014). The molecular biology and pathophysiology of vascular calcification. Postgrad Med, 126 (2): 54–64

    Article  PubMed  Google Scholar 

  72. McConnell B B, Yang V W (2010). Mammalian Krüppel-like factors in health and diseases. Physiol Rev, 90(4): 1337–1381

    Article  CAS  PubMed  Google Scholar 

  73. Mikawa T, Gourdie R G (1996). Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ. Dev Biol, 174 (2): 221–232

    Article  CAS  PubMed  Google Scholar 

  74. Mitra A K, Agrawal D K (2006). In stent restenosis: bane of the stent era. J Clin Pathol, 59(3): 232–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Newby A C, Zaltsman A B (2000). Molecular mechanisms in intimal hyperplasia. J Pathol, 190(3): 300–309

    Article  CAS  PubMed  Google Scholar 

  76. Ohta H, Wada H, Niwa T, Kirii H, Iwamoto N, Fujii H, Saito K, Sekikawa K, Seishima M (2005). Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice. Atherosclerosis, 180(1): 11–17

    Article  CAS  PubMed  Google Scholar 

  77. Oparil S, Chen S J, Chen Y F, Durand J N, Allen L, Thompson J A (1999). Estrogen attenuates the adventitial contribution to neointima formation in injured rat carotid arteries. Cardiovasc Res, 44(3): 608–614

    Article  CAS  PubMed  Google Scholar 

  78. Orlandi A, Bennett M (2010). Progenitor cell-derived smooth muscle cells in vascular disease. Biochem Pharmacol, 79(12): 1706–1713

    Article  CAS  PubMed  Google Scholar 

  79. Owens G K (1995). Regulation of differentiation of vascular smooth muscle cells. Physiol Rev, 75 (3): 487–517

    Article  CAS  PubMed  Google Scholar 

  80. Owens G K (2007). Molecular control of vascular smooth muscle cell differentiation and phenotypic plasticity. Novartis Found Symp.; 283(174–191; discussion 91–93, 238–241

    Google Scholar 

  81. Passman J N, Dong X R, Wu S P, Maguire C T, Hogan K A, Bautch V L, Majesky M W (2008). A sonic hedgehog signaling domain in the arterial adventitia supports resident Sca1 + smooth muscle progenitor cells. Proc Natl Acad Sci USA, 105(27): 9349–9354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Plass C A, Sabdyusheva-Litschauer I, Bernhart A, Samaha E, Petnehazy O, Szentirmai E, Petrási Z, Lamin V, Pavo N, Nyolczas N, Jakab A, Murlasits Z, Bergler-Klein J, Maurer G, Gyöngyösi M (2012). Time course of endothelium-dependent and-independent coronary vasomotor response to coronary balloons and stents. Comparison of plain and drug-eluting balloons and stents. JACC Cardiovasc Interv, 5(7): 741–751

    Article  PubMed  Google Scholar 

  83. Psaltis P J, Harbuzariu A, Delacroix S, Holroyd E W, Simari R D (2011). Resident vascular progenitor cells–diverse origins, phenotype, and function. J Cardiovasc Transl Res, 4(2): 161–176

    Article  PubMed  Google Scholar 

  84. Rao M S, Anderson D J (1997). Immortalization and controlled in vitro differentiation of murine multipotent neural crest stem cells. J Neurobiol, 32(7): 722–746

    Article  CAS  PubMed  Google Scholar 

  85. Regan C P, Adam P J, Madsen C S, Owens G K (2000). Molecular mechanisms of decreased smooth muscle differentiation marker expression after vascular injury. J Clin Invest, 106(9): 1139–1147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Reznikoff C A, Brankow D W, Heidelberger C (1973). Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res, 33(12): 3231–3238

    CAS  PubMed  Google Scholar 

  87. Rodriguez-Menocal L, St-Pierre M, Wei Y, Khan S, Mateu D, Calfa M, Rahnemai-Azar A A, Striker G, Pham S M, Vazquez-Padron R I (2009). The origin of post-injury neointimal cells in the rat balloon injury model. Cardiovasc Res, 81(1): 46–53

    Article  CAS  PubMed  Google Scholar 

  88. Rohwedder I, Montanez E, Beckmann K, Bengtsson E, Dunér P, Nilsson J, Soehnlein O, Fässler R (2012). Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation. EMBO Mol Med, 4(7): 564–576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Rudnicki MA, Sawtell NM, Reuhl K R, Berg R, Craig J C, Jardine K, Lessard J L, McBurney M W (1990). Smooth muscle actin expression during P19 embryonal carcinoma differentiation in cell culture. J Cell Physiol, 142(1): 89–98

    Article  CAS  PubMed  Google Scholar 

  90. Rzucidlo E M, Martin K A, Powell R J (2007). Regulation of vascular smooth muscle cell differentiation. J Vasc Surg, 45 (Suppl A): A25–32

    Article  PubMed  Google Scholar 

  91. Sartore S, Chiavegato A, Faggin E, Franch R, Puato M, Ausoni S, Pauletto P (2001). Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant. Circ Res, 89(12): 1111–1121

    Article  CAS  PubMed  Google Scholar 

  92. Schober A (2008). Chemokines in vascular dysfunction and remodeling. Arterioscler Thromb Vasc Biol, 28(11): 1950–1959

    Article  CAS  PubMed  Google Scholar 

  93. Schwartz S M, Stemerman M B, Benditt E P (1975). The aortic intima. II. Repair of the aortic lining after mechanical denudation. Am J Pathol, 81(1): 15–42

    CAS  PubMed  Google Scholar 

  94. Scott N A, Cipolla G D, Ross C E, Dunn B, Martin F H, Simonet L, Wilcox J N (1996). Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries. Circulation, 93(12): 2178–2187

    Article  CAS  PubMed  Google Scholar 

  95. Shanahan C M, Crouthamel M H, Kapustin A, Giachelli C M (2011). Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res, 109(6): 697–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Shankman L S, Gomez D, Cherepanova O A, Salmon M, Alencar G F, Haskins R M, Swiatlowska P, Newman A A, Greene E S, Straub A C, Isakson B, Randolph G J, Owens G K (2015). KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med, 21(6): 628–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Shi N, Chen S Y (2016). Smooth muscle cell differentiation: model systems, regulatory mechanisms, and vascular diseases. J Cell Physiol, 231(4): 777–787

    Article  CAS  PubMed  Google Scholar 

  98. Shi N, Xie W B, Chen S Y (2012). Cell division cycle 7 is a novel regulator of transforming growth factor-β-induced smooth muscle cell differentiation. J Biol Chem, 287(9): 6860–6867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Shi Y, O’Brien J E, Fard A, Mannion J D, Wang D, Zalewski A (1996). Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation, 94(7): 1655–1664

    Article  CAS  PubMed  Google Scholar 

  100. Shikatani E A, Chandy M, Besla R, Li C C, Momen A, El-Mounayri O, Robbins C S, Husain M (2016). c-Myb Regulates Proliferation and Differentiation of Adventitial Sca1 + Vascular Smooth Muscle Cell Progenitors by Transactivation of Myocardin. Arterioscler Thromb Vasc Biol, 36(7): 1367–1376

    Article  CAS  PubMed  Google Scholar 

  101. Speer M Y, Yang H Y, Brabb T, Leaf E, Look A, Lin WL, Frutkin A, Dichek D, Giachelli C M (2009). Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res, 104(6): 733–741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Spin J M, Nallamshetty S, Tabibiazar R, Ashley E A, King J Y, Chen M, Tsao P S, Quertermous T (2004). Transcriptional profiling of in vitro smooth muscle cell differentiation identifies specific patterns of gene and pathway activation. Physiol Genomics, 19(3): 292–302

    Article  CAS  PubMed  Google Scholar 

  103. Steinbach S K, Husain M (2016). Vascular smooth muscle cell differentiation from human stem/progenitor cells. Methods, 101: 85–92.

    Article  CAS  PubMed  Google Scholar 

  104. Steitz S A, Speer MY, Curinga G, Yang H Y, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli C M (2001). Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res, 89(12): 1147–1154

    Article  CAS  PubMed  Google Scholar 

  105. Stemerman M B, Ross R (1972). Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study. J Exp Med, 136(4): 769–789

    CAS  PubMed  Google Scholar 

  106. Sun Y, Byon C H, Yuan K, Chen J, Mao X, Heath J M, Javed A, Zhang K, Anderson P G, Chen Y (2012). Smooth muscle cellspecific runx2 deficiency inhibits vascular calcification. Circ Res, 111(5): 543–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Swirski F K, Nahrendorf M (2014). Do vascular smooth muscle cells differentiate to macrophages in atherosclerotic lesions? Circ Res, 115(7): 605–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Tabas I, García-Cardeña G, Owens G K (2015). Recent insights into the cellular biology of atherosclerosis. J Cell Biol, 209(1): 13–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tamguney T, Stokoe D (2007). New insights into PTEN. J Cell Sci, 120(Pt 23): 4071–4079

    Article  CAS  PubMed  Google Scholar 

  110. Tang Z, Wang A, Yuan F, Yan Z, Liu B, Chu J S, Helms J A, Li S (2012). Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun, 3(2): 875

    Article  PubMed  CAS  Google Scholar 

  111. Torsney E, Xu Q (2011). Resident vascular progenitor cells. J Mol Cell Cardiol, 50(2): 304–311

    Article  CAS  PubMed  Google Scholar 

  112. Tyson K L, Reynolds J L, McNair R, Zhang Q, Weissberg P L, Shanahan C M (2003). Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol, 23(3): 489–494

    Article  CAS  PubMed  Google Scholar 

  113. Vazquez F, Ramaswamy S, Nakamura N, Sellers W R (2000). Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol, 20(14): 5010–5018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Vengrenyuk Y, Nishi H, Long X, Ouimet M, Savji N, Martinez F O, Cassella C P, Moore K J, Ramsey S A, Miano J M, Fisher E A (2015). Cholesterol loading reprograms the microRNA-143/145- myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype. Arterioscler Thromb Vasc Biol, 35(3): 535–546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Vilahur G, Badimon L (2013). Antiplatelet properties of natural products. Vascul Pharmacol, 59(3-4): 67–75

    Article  CAS  PubMed  Google Scholar 

  116. Virmani R, Kolodgie F D, Burke A P, Farb A, Schwartz S M (2000). Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol, 20(5): 1262–1275

    Article  CAS  PubMed  Google Scholar 

  117. Wang C C, Gurevich I, Draznin B (2003a). Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways. Diabetes, 52(10): 2562–2569

    Article  CAS  PubMed  Google Scholar 

  118. Wang D Z, Olson E N (2004). Control of smooth muscle development by the myocardin family of transcriptional coactivators. Curr Opin Genet Dev, 14(5): 558–566

    Article  CAS  PubMed  Google Scholar 

  119. Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadière C, Rénia L, Johnson J L, Tharaux P L, Tedgui A, Mallat Z (2010). TGF-beta activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest, 120(2): 422–432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Wang Y, Krishna S, Walker P J, Norman P, Golledge J (2013). Transforming growth factor-β and abdominal aortic aneurysms. Cardiovasc Pathol, 22(2): 126–132

    Article  PubMed  CAS  Google Scholar 

  121. Wang Z, Wang D Z, Pipes G C, Olson E N (2003b). Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci USA, 100(12): 7129–7134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Xiao Q, Zeng L, Zhang Z, Hu Y, Xu Q (2007). Stem cell-derived Sca-1 + progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin alpha1/beta1/alphav and PDGF receptor pathways. Am J Physiol Cell Physiol, 292(1): C342–C352

    Article  CAS  PubMed  Google Scholar 

  123. Xiao Q, Zeng L, Zhang Z, Margariti A, Ali Z A, Channon KM, Xu Q, Hu Y (2006). Sca-1 + progenitors derived from embryonic stem cells differentiate into endothelial cells capable of vascular repair after arterial injury. Arterioscler Thromb Vasc Biol, 26(10): 2244–2251

    Article  CAS  PubMed  Google Scholar 

  124. Xie C Q, Huang H, Wei S, Song L S, Zhang J, Ritchie R P, Chen L, Zhang M, Chen Y E (2009). A comparison of murine smooth muscle cells generated from embryonic versus induced pluripotent stem cells. Stem Cells Dev, 18(5): 741–748

    Article  CAS  PubMed  Google Scholar 

  125. Xu Q (2007). Progenitor cells in vascular repair. Curr Opin Lipidol, 18(5): 534–539

    Article  CAS  PubMed  Google Scholar 

  126. Yang L, Geng Z, Nickel T, Johnson C, Gao L, Dutton J, Hou C, Zhang J (2016). Differentiation of Human Induced-Pluripotent Stem Cells into Smooth-Muscle Cells: Two Novel Protocols. PLoS One, 11(1): e0147155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Yoshida T, Kaestner K H, Owens G K (2008). Conditional deletion of Krüppel-like factor 4 delays downregulation of smooth muscle cell differentiation markers but accelerates neointimal formation following vascular injury. Circ Res, 102(12): 1548–1557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Yoshida T, Owens G K (2005). Molecular determinants of vascular smooth muscle cell diversity. Circ Res, 96(3): 280–291

    Article  CAS  PubMed  Google Scholar 

  129. Zengin E, Chalajour F, Gehling UM, Ito WD, Treede H, Lauke H, Weil J, Reichenspurner H, Kilic N, Ergün S (2006). Vascular wall resident progenitor cells: a source for postnatal vasculogenesis. Development, 133(8): 1543–1551

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China (Nos. 91539110, U1601219), National Key Research and Development Program of China (2016YFC1300600), Scientific Grant of Guangzhou (201604020131), Scientific Grants of Guangdong (Nos. 2015B020225002 and 2015A050502018). This work was partly supported by Connecticut Innovations Established Investigator Award 14-SCB-YALE-17, NIH grants R01 HL109420, HL115148 and HL136507.

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  1. Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Yujie Deng, Caixia Lin & Wang Min

  2. Department of Pathology and the Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT, 06520, USA

    Huanjiao Jenny Zhou & Wang Min

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  1. Yujie Deng
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  2. Caixia Lin
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Correspondence to Wang Min.

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Deng, Y., Lin, C., Zhou, H.J. et al. Smooth muscle cell differentiation: Mechanisms and models for vascular diseases. Front. Biol. 12, 392–405 (2017). https://doi.org/10.1007/s11515-017-1473-z

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