Altered smooth muscle cell force generation as a driver of thoracic aortic aneurysms and dissections

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 37, Issue 1, 2017, Pages 26-34

  Milewicz, Dianna M ^a   Trybus, Kathleen M ^b   Guo, Dong Chuan ^a   Sweeney, H Lee ^c   Regalado, Ellen ^a   Kamm, Kristine ^d   Stull, James T ^d  

^a UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF VERMONT   (United States)

^c UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF TEXAS AT DALLAS   (United States)

Author keywords

aortic aneurysm; aortic dissection; Marfan syndrome; mutation; thoracic aorta; vascular smooth muscle cells

Indexed keywords

ALPHA ACTININ 2; CYCLIC GMP; ELASTIN; FIBRILLIN 1; MYOSIN HEAVY CHAIN; MYOSIN LIGHT CHAIN KINASE; ACTA2 PROTEIN, HUMAN; ACTIN; CALCIUM BINDING PROTEIN; CYCLIC GMP DEPENDENT PROTEIN KINASE 1; GENETIC MARKER; MYH11 PROTEIN, HUMAN; MYLK PROTEIN, HUMAN; PRKG1 PROTEIN, HUMAN;

AORTA DISSECTION; AORTIC SMOOTH MUSCLE CELL; EXTRACELLULAR MATRIX; FOCAL ADHESION; GENETIC PREDISPOSITION; HUMAN; LOSS OF FUNCTION MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; REVIEW; SMOOTH MUSCLE CONTRACTION; THORACIC AORTA ANEURYSM; ANIMAL; DISSECTING ANEURYSM; GENETIC MARKER; GENETIC SCREENING; GENETICS; HEREDITY; LESIONS AND DEFECTS; MECHANOTRANSDUCTION; METABOLISM; MUTATION; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PULSATILE FLOW; SMOOTH MUSCLE CELL; VASCULAR SMOOTH MUSCLE; VASOCONSTRICTION;

ACTINS; ANEURYSM, DISSECTING; ANIMALS; AORTIC ANEURYSM, THORACIC; CALCIUM-BINDING PROTEINS; CYCLIC GMP-DEPENDENT PROTEIN KINASE TYPE I; DILATATION, PATHOLOGIC; ELASTIN; GENETIC MARKERS; GENETIC TESTING; HEREDITY; HUMANS; MECHANOTRANSDUCTION, CELLULAR; MUSCLE, SMOOTH, VASCULAR; MUTATION; MYOCYTES, SMOOTH MUSCLE; MYOSIN HEAVY CHAINS; MYOSIN-LIGHT-CHAIN KINASE; PHENOTYPE; PULSATILE FLOW; VASOCONSTRICTION;

EID: 84996799349     PISSN: 10795642     EISSN: 15244636     Source Type: Journal    
DOI: 10.1161/ATVBAHA.116.303229     Document Type: Review

References (76)

1. LeMaire SA, Russell L, Epidemiology of thoracic aortic dissection. Nat Rev Cardiol 2011 8 103 113. doi: 10.1038/nrcardio.2010.187
2. Howard DP, Banerjee A, Fairhead JF, Perkins J, Silver LE, Rothwell PM, Oxford Vascular Study Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford Vascular Study. Circulation 2013 127 2031 2037. doi: 10.1161/CIRCULATIONAHA.112.000483
3. Sakai LY, Keene DR, Renard M, De Backer J, FBN1: The disease-causing gene for Marfan syndrome and other genetic disorders. Gene 2016 591 279 291. doi: 10.1016/j.gene.2016.07.033
4. Guo DC, Pannu H, Tran-Fadulu V, Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet 2007 39 1488 1493. doi: 10.1038/ng.2007.6
5. Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F, Wegman M, Glancy L, Gasc JM, Brunotte F, Bruneval P, Wolf JE, Michel JB, Jeunemaitre X, Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Nat Genet 2006 38 343 349. doi: 10.1038/ng1721
6. Wang L, Guo DC, Cao J, Gong L, Kamm KE, Regalado E, Li L, Shete S, He WQ, Zhu MS, Offermanns S, Gilchrist D, Elefteriades J, Stull JT, Milewicz DM, Mutations in myosin light chain kinase cause familial aortic dissections. Am J Hum Genet 2010 87 701 707. doi: 10.1016/j.ajhg.2010.10.006
7. Guo DC, Regalado E, Casteel DE, GenTAC Registry Consortium; National Heart, Lung, and Blood Institute Grand Opportunity Exome Sequencing Project Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections. Am J Hum Genet 2013 93 398 404. doi: 10.1016/j.ajhg.2013.06.019
8. Barbier M, Gross MS, Aubart M, MFAP5 loss-of-function mutations underscore the involvement of matrix alteration in the pathogenesis of familial thoracic aortic aneurysms and dissections. Am J Hum Genet 2014 95 736 743. doi: 10.1016/j.ajhg.2014.10.018
9. Guo DC, Regalado ES, Gong L, University of Washington Center for Mendelian Genomics LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections. Circ Res 2016 118 928 934. doi: 10.1161/CIRCRESAHA.115.307130
10. Mizuguchi T, Collod-Beroud G, Akiyama T, Heterozygous TGFBR2 mutations in Marfan syndrome. Nat Genet 2004 36 855 860. doi: 10.1038/ng1392
11. Loeys BL, Schwarze U, Holm T, Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006 355 788 798. doi: 10.1056/NEJMoa055695
12. Pannu H, Fadulu VT, Chang J, Lafont A, Hasham SN, Sparks E, Giampietro PF, Zaleski C, Estrera AL, Safi HJ, Shete S, Willing MC, Raman CS, Milewicz DM, Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 2005 112 513 520. doi: 10.1161/CIRCULATIONAHA.105.537340
13. Regalado ES, Guo DC, Villamizar C, Avidan N, Gilchrist D, McGillivray B, Clarke L, Bernier F, Santos-Cortez RL, Leal SM, Bertoli-Avella AM, Shendure J, Rieder MJ, Nickerson DA, Milewicz DM, NHLBI GO Exome Sequencing Project Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms. Circ Res 2011 109 680 686. doi: 10.1161/CIRCRESAHA.111.248161
14. Boileau C, Guo DC, Hanna N, National Heart, Lung, and Blood Institute (NHLBI) Go Exome Sequencing Project TGFB2 mutations cause familial thoracic aortic aneurysms and dissections associated with mild systemic features of Marfan syndrome. Nat Genet 2012 44 916 921. doi: 10.1038/ng.2348
15. Bertoli-Avella AM, Gillis E, Morisaki H, Mutations in a TGF-β ligand, TGFB3, cause syndromic aortic aneurysms and dissections. J Am Coll Cardiol 2015 65 1324 1336. doi: 10.1016/j.jacc.2015.01.040
16. Guo DC, Gong L, Regalado ES, GenTAC Investigators, National Heart, Lung, and Blood Institute Go Exome Sequencing Project; Montalcino Aortic Consortium MAT2A mutations predispose individuals to thoracic aortic aneurysms. Am J Hum Genet 2015 96 170 177. doi: 10.1016/j.ajhg.2014.11.015
17. Kuang SQ, Medina-Martinez O, Guo DC, FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. J Clin Invest 2016 126 948 961. doi: 10.1172/JCI83778
18. Milewicz DM, Guo DC, Tran-Fadulu V, Lafont AL, Papke CL, Inamoto S, Kwartler CS, Pannu H, Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction. Annu Rev Genomics Hum Genet 2008 9 283 302. doi: 10.1146/annurev.genom.8.080706.092303
19. Humphrey JD, Milewicz DM, Tellides G, Schwartz MA, Cell biology. Dysfunctional mechanosensing in aneurysms. Science 2014 344 477 479. doi: 10.1126/science.1253026
20. Humphrey JD, Schwartz MA, Tellides G, Milewicz DM, Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections. Circ Res 2015 116 1448 1461. doi: 10.1161/CIRCRESAHA.114.304936
21. LeMaire SA, McDonald ML, Guo DC, Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet 2011 43 996 1000. doi: 10.1038/ng.934
22. Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA, Weight lifting and aortic dissection: more evidence for a connection. Cardiology 2007 107 103 106. doi: 10.1159/000094530
23. Fisher SA, Vascular smooth muscle phenotypic diversity and function. Physiol Genomics 2010 42A 169 187. doi: 10.1152/physiolgenomics.00111.2010
24. Kim HR, Gallant C, Leavis PC, Gunst SJ, Morgan KG, Cytoskeletal remodeling in differentiated vascular smooth muscle is actin isoform dependent and stimulus dependent. Am J Physiol Cell Physiol 2008 295 C768 C778. doi: 10.1152/ajpcell.00174.2008
25. Cipolla MJ, Gokina NI, Osol G, Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior. FASEB J 2002 16 72 76. doi: 10.1096/cj.01-0104hyp
26. Gunst SJ, Zhang W, Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am J Physiol Cell Physiol 2008 295 C576 C587. doi: 10.1152/ajpcell.00253.2008
27. McGregor E, Kempster L, Wait R, Gosling M, Dunn MJ, Powell JT, F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress: a proteonomic approach. Mol Cell Proteomics 2004 3 115 124. doi: 10.1074/mcp.M300046-MCP200
28. van den Akker J, Schoorl MJ, Bakker EN, Vanbavel E, Small artery remodeling: current concepts and questions. J Vasc Res 2010 47 183 202. doi: 10.1159/000255962
29. Fatigati V, Murphy RA, Actin and tropomyosin variants in smooth muscles. Dependence on tissue type. J Biol Chem 1984 259 14383 14388
30. Drew JS, Murphy RA, Actin isoform expression, cellular heterogeneity, and contractile function in smooth muscle. Can J Physiol Pharmacol 1997 75 869 877
31. Stromer MH, Mayes MS, Bellin RM, Use of actin isoform-specific antibodies to probe the domain structure in three smooth muscles. Histochem Cell Biol 2002 118 291 299. doi: 10.1007/s00418-002-0453-8
32. Zhang W, Wu Y, Du L, Tang DD, Gunst SJ, Activation of the Arp2/3 complex by N-WASp is required for actin polymerization and contraction in smooth muscle. Am J Physiol Cell Physiol 2005 288 C1145 C1160. doi: 10.1152/ajpcell.00387.2004
33. Chen X, Pavlish K, Benoit JN, Myosin phosphorylation triggers actin polymerization in vascular smooth muscle. Am J Physiol Heart Circ Physiol 2008 295 H2172 H2177. doi: 10.1152/ajpheart.91437.2007
34. Tang DD, Anfinogenova Y, Physiologic properties and regulation of the actin cytoskeleton in vascular smooth muscle. J Cardiovasc Pharmacol Ther 2008 13 130 140. doi: 10.1177/1074248407313737
35. Zhao R, Du L, Huang Y, Wu Y, Gunst SJ, Actin depolymerization factor/cofilin activation regulates actin polymerization and tension development in canine tracheal smooth muscle. J Biol Chem 2008 283 36522 36531. doi: 10.1074/jbc.M805294200
36. Kim HR, Leavis PC, Graceffa P, Gallant C, Morgan KG, A new method for direct detection of the sites of actin polymerization in intact cells and its application to differentiated vascular smooth muscle. Am J Physiol Cell Physiol 2010 299 C988 C993. doi: 10.1152/ajpcell.00210.2010
37. Kamm KE, Stull JT, The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol 1985 25 593 620. doi: 10.1146/annurev.pa.25.040185.003113
38. Somlyo AP, Somlyo AV, Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 2003 83 1325 1358. doi: 10.1152/physrev.00023.2003
39. Kamm KE, Stull JT, Dedicated myosin light chain kinases with diverse cellular functions. J Biol Chem 2001 276 4527 4530. doi: 10.1074/jbc.R000028200
40. He WQ, Peng YJ, Zhang WC, Lv N, Tang J, Chen C, Zhang CH, Gao S, Chen HQ, Zhi G, Feil R, Kamm KE, Stull JT, Gao X, Zhu MS, Myosin light chain kinase is central to smooth muscle contraction and required for gastrointestinal motility in mice. Gastroenterology 2008 135 610 620. doi: 10.1053/j.gastro.2008.05.032
41. Zhang WC, Peng YJ, Zhang GS, Myosin light chain kinase is necessary for tonic airway smooth muscle contraction. J Biol Chem 2010 285 5522 5531. doi: 10.1074/jbc.M109.062836
42. Wendt T, Taylor D, Messier T, Trybus KM, Taylor KA, Visualization of head-head interactions in the inhibited state of smooth muscle myosin. J Cell Biol 1999 147 1385 1390
43. Lowey S, Trybus KM, Common structural motifs for the regulation of divergent class II myosins. J Biol Chem 2010 285 16403 16407. doi: 10.1074/jbc.R109.025551
44. Davis EC, Smooth muscle cell to elastic lamina connections in developing mouse aorta. Role in aortic medial organization. Lab Invest 1993 68 89 99
45. Berry CL, Greenwald SE, Rivett JF, Static mechanical properties of the developing and mature rat aorta. Cardiovasc Res 1975 9 669 678
46. Guo DC, Papke CL, Tran-Fadulu V, Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet 2009 84 617 627. doi: 10.1016/j.ajhg.2009.04.007
47. Morisaki H, Akutsu K, Ogino H, Kondo N, Yamanaka I, Tsutsumi Y, Yoshimuta T, Okajima T, Matsuda H, Minatoya K, Sasaki H, Tanaka H, Ishibashi-Ueda H, Morisaki T, Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD). Hum Mutat 2009 30 1406 1411. doi: 10.1002/humu.21081
48. Milewicz DM, Kwartler CS, Papke CL, Regalado ES, Cao J, Reid AJ, Genetic variants promoting smooth muscle cell proliferation can result in diffuse and diverse vascular diseases: evidence for a hyperplastic vasculomyopathy. Genet Med 2010 12 196 203. doi: 10.1097/GIM.0b013e3181cdd687
49. Milewicz DM, Carlson AA, Regalado ES, Genetic testing in aortic aneurysm disease: PRO. Cardiol Clin 2010 28 191 197. doi: 10.1016/j.ccl.2010.01.017
50. Regalado ES, Guo DC, Prakash S, Montalcino Aortic Consortium Aortic disease presentation and outcome associated with ACTA2 mutations. Circ Cardiovasc Genet 2015 8 457 464. doi: 10.1161/CIRCGENETICS.114.000943
51. Lu H, Fagnant PM, Bookwalter CS, Joel P, Trybus KM, Vascular disease-causing mutation R258C in ACTA2 disrupts actin dynamics and interaction with myosin. Proc Natl Acad Sci U S A 2015 112 E4168 E4177. doi: 10.1073/pnas.1507587112
52. Pannu H, Tran-Fadulu V, Papke CL, Scherer S, Liu Y, Presley C, Guo D, Estrera AL, Safi HJ, Brasier AR, Vick GW, Marian AJ, Raman CS, Buja LM, Milewicz DM, MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. Hum Mol Genet 2007 16 2453 2462. doi: 10.1093/hmg/ddm201
53. Harakalova M, van Der Smagt J, de Kovel CG, Incomplete segregation of MYH11 variants with thoracic aortic aneurysms and dissections and patent ductus arteriosus. Eur J Hum Genet 2013 21 487 493. doi: 10.1038/ejhg.2012.206
54. Kuang SQ, Guo DC, Prakash SK, GenTAC Investigators Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections. PLoS Genet 2011 7 e1002118. doi: 10.1371/journal.pgen.1002118
55. Kwartler CS, Chen J, Thakur D, Li S, Baskin K, Wang S, Wang ZV, Walker L, Hill JA, Epstein HF, Taegtmeyer H, Milewicz DM, Overexpression of smooth muscle myosin heavy chain leads to activation of the unfolded protein response and autophagic turnover of thick filament-associated proteins in vascular smooth muscle cells. J Biol Chem 2014 289 14075 14088. doi: 10.1074/jbc.M113.499277
56. Kuang SQ, Kwartler CS, Byanova KL, Pham J, Gong L, Prakash SK, Huang J, Kamm KE, Stull JT, Sweeney HL, Milewicz DM, Rare, nonsynonymous variant in the smooth muscle-specific isoform of myosin heavy chain, MYH11, R247C, alters force generation in the aorta and phenotype of smooth muscle cells. Circ Res 2012 110 1411 1422. doi: 10.1161/CIRCRESAHA.111.261743
57. Wallace KN, Dolan AC, Seiler C, Smith EM, Yusuff S, Chaille-Arnold L, Judson B, Sierk R, Yengo C, Sweeney HL, Pack M, Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion of the zebrafish intestine. Dev Cell 2005 8 717 726. doi: 10.1016/j.devcel.2005.02.015
58. Abrams J, Einhorn Z, Seiler C, Zong AB, Sweeney HL, Pack M, Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish. Dis Model Mech 2016 9 529 540. doi: 10.1242/dmm.023309
59. Herring BP, El-Mounayri O, Gallagher PJ, Yin F, Zhou J, Regulation of myosin light chain kinase and telokin expression in smooth muscle tissues. Am J Physiol Cell Physiol 2006 291 C817 C827. doi: 10.1152/ajpcell.00198.2006
60. Gao N, Huang J, He W, Zhu M, Kamm KE, Stull JT, Signaling through myosin light chain kinase in smooth muscles. J Biol Chem 2013 288 7596 7605. doi: 10.1074/jbc.M112.427112
61. Francis SH, Busch JL, Corbin JD, Sibley D, cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 2010 62 525 563. doi: 10.1124/pr.110.002907
62. Surks HK, cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms. Circ Res 2007 101 1078 1080. doi: 10.1161/CIRCRESAHA.107.165779
63. Hofmann F, Bernhard D, Lukowski R, Weinmeister P, cGMP regulated protein kinases (cGK). Handb Exp Pharmacol 2009 137 62
64. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, Wang GX, Korth M, Aszódi A, Andersson KE, Krombach F, Mayerhofer A, Ruth P, Fässler R, Hofmann F, Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 1998 17 3045 3051. doi: 10.1093/emboj/17.11.3045
65. Blanton RM, Takimoto E, Aronovitz M, Thoonen R, Kass DA, Karas RH, Mendelsohn ME, Mutation of the protein kinase I alpha leucine zipper domain produces hypertension and progressive left ventricular hypertrophy: a novel mouse model of age-dependent hypertensive heart disease. J Gerontol A Biol Sci Med Sci 2013 68 1351 1355. doi: 10.1093/gerona/glt042
66. Hollister DW, Godfrey M, Sakai LY, Pyeritz RE, Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med 1990 323 152 159. doi: 10.1056/NEJM199007193230303
67. Milewicz DM, Pyeritz RE, Crawford ES, Byers PH, Marfan syndrome: defective synthesis, secretion, and extracellular matrix formation of fibrillin by cultured dermal fibroblasts. J Clin Invest 1992 89 79 86. doi: 10.1172/JCI115589
68. Handford PA, Downing AK, Reinhardt DP, Sakai LY, Fibrillin: from domain structure to supramolecular assembly. Matrix Biol 2000 19 457 470
69. Bunton TE, Biery NJ, Myers L, Gayraud B, Ramirez F, Dietz HC, Phenotypic alteration of vascular smooth muscle cells precedes elastolysis in a mouse model of Marfan syndrome. Circ Res 2001 88 37 43
70. Yang HH, van Breemen C, Chung AW, Vasomotor dysfunction in the thoracic aorta of Marfan syndrome is associated with accumulation of oxidative stress. Vascul Pharmacol 2010 52 37 45. doi: 10.1016/j.vph.2009.10.005
71. Inamoto S, Kwartler CS, Lafont AL, TGFBR2 mutations alter smooth muscle cell phenotype and predispose to thoracic aortic aneurysms and dissections. Cardiovasc Res 2010 88 520 529. doi: 10.1093/cvr/cvq230
72. Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T, TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development 1997 124 2659 2670
73. Chen S, Lechleider RJ, Transforming growth factor-beta-induced differentiation of smooth muscle from a neural crest stem cell line. Circ Res 2004 94 1195 1202. doi: 10.1161/01.RES.0000126897.41658.81
74. Prakash SK, LeMaire SA, Guo DC, Russell L, Regalado ES, Golabbakhsh H, Johnson RJ, Safi HJ, Estrera AL, Coselli JS, Bray MS, Leal SM, Milewicz DM, Belmont JW, Rare copy number variants disrupt genes regulating vascular smooth muscle cell adhesion and contractility in sporadic thoracic aortic aneurysms and dissections. Am J Hum Genet 2010 87 743 756. doi: 10.1016/j.ajhg.2010.09.015
75. Doyle JJ, Doyle AJ, Wilson NK, A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome. eLIFE 2015 4 e08648. doi: 10.7554/eLife.08648
76. Simpson CF, Taylor WJ, Effect of hydralazine on aortic rupture induced by B-aminopropionitrile in turkeys. Circulation 1982 65 704 708