Vascular smooth muscle LRP6 limits arteriosclerotic calcification in diabetic LDLR-/- mice by restraining noncanonical Wnt signals

Circulation Research

Volumn 117, Issue 2, 2015, Pages 142-156

  Cheng, Su Li ^a   Ramachandran, Bindu ^a   Behrmann, Abraham ^a   Shao, Jian Su ^b   Mead, Megan ^a   Smith, Carolyn ^a   Krchma, Karen ^c   Arredondo, Yoanna Bello ^a   Kovacs, Attila ^c   Kapoor, Kapil ^a   Brill, Laurence M ^a   Perera, Ranjan ^a   Williams, Bart O ^d   Towler, Dwight A ^a  

^a BURNHAM INSTITUTE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c WASHINGTON UNIVERSITY   (United States)

^d VAN ANDEL RESEARCH INSTITUTE   (United States)

Author keywords

arteriosclerosis; LRP6; signal transduction; type 2 diabetes mellitus; USF1; vascular calcification; Wnt

Indexed keywords

ALKALINE PHOSPHATASE; CALCIUM; FRIZZLED PROTEIN; GLUCOSE; HISTONE H3; INSULIN; LIPID; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 6; MESSENGER RNA; N(G),N(G) DIMETHYLARGININE; OSTEOPONTIN; PROTEIN ARGININE METHYLTRANSFERASE; SMALL INTERFERING RNA; UPSTREAM STIMULATORY FACTOR; UPSTREAM STIMULATORY FACTOR 1; UPSTREAM STIMULATORY FACTOR 2; WNT PROTEIN; ARGININE; CELL SURFACE RECEPTOR; FAT INTAKE; FZD10 PROTEIN, MOUSE; HISTONE; LOW DENSITY LIPOPROTEIN RECEPTOR; LRP6 PROTEIN, MOUSE; N,N-DIMETHYLARGININE; PRMT1 PROTEIN, MOUSE; PTDSR PROTEIN, MOUSE; SPP1 PROTEIN, MOUSE; USF1 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTERIAL STIFFNESS; ARTERY CALCIFICATION; ARTICLE; BLOOD VESSEL CALCIFICATION; BODY COMPOSITION; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; COMPARATIVE STUDY; CONTROLLED STUDY; DIABETIC ANGIOPATHY; FEEDER CELL; GENE EXPRESSION; GENETIC TRANSFECTION; GENOTYPE; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; INSULIN RESISTANCE; LIPID BLOOD LEVEL; LIPID DIET; MALE; MASS SPECTROMETRY; MOUSE; NONHUMAN; PHENOTYPE; PRIMARY CULTURE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN DNA INTERACTION; PROTEIN EXPRESSION; PULSE WAVE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TRANSCRIPTION INITIATION; UPREGULATION; VASCULAR SMOOTH MUSCLE; WESTERN BLOTTING; WNT SIGNALING PATHWAY; ADVERSE EFFECTS; ANALOGS AND DERIVATIVES; ANIMAL; ARTERIOSCLEROSIS; BIOSYNTHESIS; CALCINOSIS; COMPLICATION; DEFICIENCY; EXPERIMENTAL DIABETES MELLITUS; FAT INTAKE; GENE EXPRESSION REGULATION; GENETICS; KNOCKOUT MOUSE; METABOLISM; PARACRINE SIGNALING; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PROTEIN ANALYSIS; SMOOTH MUSCLE CELL;

ANIMALS; ARGININE; ARTERIOSCLEROSIS; CALCINOSIS; DIABETES MELLITUS, EXPERIMENTAL; DIETARY FATS; FRIZZLED RECEPTORS; GENE EXPRESSION REGULATION; HISTONES; LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-6; MALE; MICE; MICE, KNOCKOUT; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; OSTEOPONTIN; PARACRINE COMMUNICATION; PROTEIN INTERACTION MAPPING; PROTEIN-ARGININE N-METHYLTRANSFERASES; RECEPTORS, CELL SURFACE; RECEPTORS, LDL; UPSTREAM STIMULATORY FACTORS; VASCULAR STIFFNESS; WNT SIGNALING PATHWAY;

EID: 84937714875     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.117.306712     Document Type: Article

References (62)

1. Thompson B, Towler DA. Arterial calcification and bone physiology: role of the bone-vascular axis. Nat Rev Endocrinol. 2012; 8: 529-543. doi: 10.1038/nrendo.2012.36
2. Demer LL, Tintut Y. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler Thromb Vasc Biol. 2014; 34: 715-723. doi: 10.1161/ATVBAHA.113.302070
3. Boström KI, Jumabay M, Matveyenko A, Nicholas SB, Yao Y. Activation of vascular bone morphogenetic protein signaling in diabetes mellitus. Circ Res. 2011; 108: 446-457. doi: 10.1161/CIRCRESAHA.110.236596
4. Woldt E, Terrand J, Mlih M, et al. The nuclear hormone receptor PPARγ counteracts vascular calcification by inhibiting Wnt5a signalling in vascular smooth muscle cells. Nat Commun. 2012; 3: 1077. doi: 10.1038/ncomms2087
5. Shao JS, Cheng SL, Pingsterhaus JM, Charlton-Kachigian N, Loewy AP, Towler DA. Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. J Clin Invest. 2005; 115: 1210-1220. doi: 10.1172/JCI24140
6. Beazley KE, Nurminsky D, Lima F, Gandhi C, Nurminskaya MV. Wnt16 attenuates TGFβ-induced chondrogenic transformation in vascular smooth muscle. Arterioscler Thromb Vasc Biol. 2015; 35: 573-579. doi: 10.1161/ATVBAHA.114.304393
7. Derwall M, Malhotra R, Lai CS, Beppu Y, Aikawa E, Seehra JS, Zapol WM, Bloch KD, Yu PB. Inhibition of bone morphogenetic protein signaling reduces vascular calcification and atherosclerosis. Arterioscler Thromb Vasc Biol. 2012; 32: 613-622. doi: 10.1161/ATVBAHA.111.242594
8. Schreyer SA, Vick C, Lystig TC, Mystkowski P, LeBoeuf RC. LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice. Am J Physiol Endocrinol Metab. 2002; 282: E207-E214
9. Cheng SL, Behrmann A, Shao JS, Ramachandran B, Krchma K, Bello Arredondo Y, Kovacs A, Mead M, Maxson R, Towler DA. Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic calcification and aortic stiffness in LDLR-deficient mice fed diabetogenic diets. Diabetes. 2014; 63: 4326-4337. doi: 10.2337/db14-0326
10. Cheng SL, Shao JS, Behrmann A, Krchma K, Towler DA. Dkk1 and MSX2-Wnt7b signaling reciprocally regulate the endothelial-mesenchymal transition in aortic endothelial cells. Arterioscler Thromb Vasc Biol. 2013; 33: 1679-1689. doi: 10.1161/ATVBAHA.113.300647
11. Tu X, Joeng KS, Nakayama KI, Nakayama K, Rajagopal J, Carroll TJ, McMahon AP, Long F. Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell. 2007; 12: 113-127. doi: 10.1016/j.devcel.2006.11.003
12. Joiner DM, Ke J, Zhong Z, Xu HE, Williams BO. LRP5 and LRP6 in development and disease. Trends Endocrinol Metab. 2013; 24: 31-39. doi: 10.1016/j.tem.2012.10.003
13. Rao TP, Kühl M. An updated overview on Wnt signaling pathways: a prelude for more. Circ Res. 2010; 106: 1798-1806. doi: 10.1161/CIRCRESAHA.110.219840
14. Esen E, Chen J, Karner CM, Okunade AL, Patterson BW, Long F. WNTLRP5 signaling induces Warburg effect through mTORC2 activation during osteoblast differentiation. Cell Metab. 2013; 17: 745-755. doi: 10.1016/j.cmet.2013.03.017
15. Grumolato L, Liu G, Mong P, Mudbhary R, Biswas R, Arroyave R, Vijayakumar S, Economides AN, Aaronson SA. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010; 24: 2517-2530. doi: 10.1101/gad.1957710
16. Rajamannan NM. The role of Lrp5/6 in cardiac valve disease: experimental hypercholesterolemia in the ApoE-/-/Lrp5-/-mice. J Cell Biochem. 2011; 112: 2987-2991. doi: 10.1002/jcb.23221
17. Joeng KS, Schumacher CA, Zylstra-Diegel CR, Long F, Williams BO. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol. 2011; 359: 222-229. doi: 10.1016/j.ydbio.2011.08.020
18. Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP. LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science. 2007; 315: 1278-1282. doi: 10.1126/science.1136370
19. Demer L, Tintut Y. The bone-vascular axis in chronic kidney disease. Curr Opin Nephrol Hypertens. 2010; 19: 349-353. doi: 10.1097/MNH.0b013e32833a3d67
20. Holtwick R, Gotthardt M, Skryabin B, Steinmetz M, Potthast R, Zetsche B, Hammer RE, Herz J, Kuhn M. Smooth muscle-selective deletion of guanylyl cyclase-A prevents the acute but not chronic effects of ANP on blood pressure. Proc Natl Acad Sci USA 2002; 99: 7142-7147. doi: 10.1073/pnas.102650499
21. Zhong Z, Baker JJ, Zylstra-Diegel CR, Williams BO. Lrp5 and Lrp6 play compensatory roles in mouse intestinal development. J Cell Biochem. 2012; 113: 31-38. doi: 10.1002/jcb.23324
22. Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A. The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue. Cell Metab. 2014; 19: 209-220. doi: 10.1016/j.cmet.2013.11.023
23. Cheng SL, Shao JS, Halstead LR, Distelhorst K, Sierra O, Towler DA. Activation of vascular smooth muscle parathyroid hormone receptor inhibits Wnt/beta-catenin signaling and aortic fibrosis in diabetic arteriosclerosis. Circ Res. 2010; 107: 271-282. doi: 10.1161/CIRCRESAHA.110.219899
24. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F. Wnt/betacatenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol. 2002; 22: 1172-1183
25. Ziemer LT, Pennica D, Levine AJ. Identification of a mouse homolog of the human BTEB2 transcription factor as a beta-catenin-independent Wnt-1-responsive gene. Mol Cell Biol. 2001; 21: 562-574. doi: 10.1128/MCB.21.2.562-574.2001
26. Laudes M, Oberhauser F, Schulte DM, Freude S, Bilkovski R, Mauer J, Rappl G, Abken H, Hahn M, Schulz O, Krone W. Visfatin/PBEF/Nampt and resistin expressions in circulating blood monocytes are differentially related to obesity and type 2 diabetes in humans. Horm Metab Res. 2010; 42: 268-273. doi: 10.1055/s-0029-1243638
27. Mayr M, Zampetaki A, Sidibe A, Mayr U, Yin X, De Souza AI, Chung YL, Madhu B, Quax PH, Hu Y, Griffiths JR, Xu Q. Proteomic and metabolomic analysis of smooth muscle cells derived from the arterial media and adventitial progenitors of apolipoprotein E-deficient mice. Circ Res. 2008; 102: 1046-1056. doi: 10.1161/CIRCRESAHA.108.174623
28. Wolak T. Osteopontin -a multi-modal marker and mediator in atherosclerotic vascular disease. Atherosclerosis. 2014; 236: 327-337. doi: 10.1016/j. atherosclerosis.2014.07.004
29. Cohen MM Jr. The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A. 2006; 140: 2646-2706. doi: 10.1002/ajmg.a.31368
30. Kubota T, Michigami T, Sakaguchi N, Kokubu C, Suzuki A, Namba N, Sakai N, Nakajima S, Imai K, Ozono K. Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd. J Bone Miner Res. 2008; 23: 1661-1671. doi: 10.1359/jbmr.080512
31. Heilmann A, Schinke T, Bindl R, Wehner T, Rapp A, Haffner-Luntzer M, Nemitz C, Liedert A, Amling M, Ignatius A. The Wnt serpentine receptor Frizzled-9 regulates new bone formation in fracture healing. PLoS One. 2013; 8: e84232. doi: 10.1371/journal.pone.0084232
32. Okamoto M, Udagawa N, Uehara S, Maeda K, Yamashita T, Nakamichi Y, Kato H, Saito N, Minami Y, Takahashi N, Kobayashi Y. Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis. Sci Rep. 2014; 4: 4493. doi: 10.1038/srep04493
33. Chang J, Sonoyama W, Wang Z, Jin Q, Zhang C, Krebsbach PH, Giannobile W, Shi S, Wang CY. Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J Biol Chem. 2007; 282: 30938-30948. doi: 10.1074/jbc.M702391200
34. Lyons JP, Mueller UW, Ji H, Everett C, Fang X, Hsieh JC, Barth AM, McCrea PD. Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/betacatenin activity in kidney epithelial cells. Exp Cell Res. 2004; 298: 369-387. doi: 10.1016/j.yexcr.2004.04.036
35. Fukukawa C, Nagayama S, Tsunoda T, Toguchida J, Nakamura Y, Katagiri T. Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma. Oncogene. 2009; 28: 1110-1120. doi: 10.1038/onc.2008.467
36. Bradley EW, Drissi MH. WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappa;B pathways. Mol Endocrinol. 2010; 24: 1581-1593. doi: 10.1210/me.2010-0037
37. Ring L, Peröbner I, Karow M, Jochum M, Neth P, Faussner A. Reporter gene HEK 293 cells and WNT/Frizzled fusion proteins as tools to study WNT signaling pathways. Biol Chem. 2011; 392: 1011-1020. doi: 10.1515/BC.2011.164
38. Surviladze Z, Waller A, Strouse JJ, Bologa C, Ursu O, Salas V, Parkinson JF, Phillips GK, Romero E, Wandinger-Ness A, Sklar LA, Schroeder C, Simpson D, Noth J, Wang J, Golden J, Aube J. A potent and selective inhibitor of cdc42 gtpase. Probe Reports From the NIH Molecular Libraries Program. Bethesda (MD); 2010
39. Yuan K, Orcholski ME, Panaroni C, Shuffle EM, Huang NF, Jiang X, Tian W, Vladar EK, Wang L, Nicolls MR, Wu JY, de Jesus Perez VA. Activation of the Wnt/planar cell polarity pathway is required for pericyte recruitment during pulmonary angiogenesis. Am J Pathol. 2015; 185: 69-84. doi: 10.1016/j.ajpath.2014.09.013
40. Bilkovski R, Schulte DM, Oberhauser F, Gomolka M, Udelhoven M, Hettich MM, Roth B, Heidenreich A, Gutschow C, Krone W, Laudes M. Role of WNT-5a in the determination of human mesenchymal stem cells into preadipocytes. J Biol Chem. 2010; 285: 6170-6178. doi: 10.1074/jbc. M109.054338
41. Bidder M, Shao JS, Charlton-Kachigian N, Loewy AP, Semenkovich CF, Towler DA. Osteopontin transcription in aortic vascular smooth muscle cells is controlled by glucose-regulated upstream stimulatory factor and activator protein-1 activities. J Biol Chem. 2002; 277: 44485-44496. doi: 10.1074/jbc.M206235200
42. Shutes A, Onesto C, Picard V, Leblond B, Schweighoffer F, Der CJ. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J Biol Chem. 2007; 282: 35666-35678. doi: 10.1074/jbc.M703571200
43. Goulet I, Gauvin G, Boisvenue S, Côtè J. Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization. J Biol Chem. 2007; 282: 33009-33021. doi: 10.1074/jbc.M704349200
44. Bedford MT, Clarke SG. Protein arginine methylation in mammals: who, what, and why. Mol Cell. 2009; 33: 1-13. doi: 10.1016/j. molcel.2008.12.013
45. Poulard C, Rambaud J, Hussein N, Corbo L, Le Romancer M. JMJD6 regulates ERa methylation on arginine. PLoS One. 2014; 9: e87982. doi: 10.1371/journal.pone.0087982
46. Chang B, Chen Y, Zhao Y, Bruick RK. JMJD6 is a histone arginine demethylase. Science. 2007; 318: 444-447. doi: 10.1126/science.1145801
47. Kolodziej S, Kuvardina ON, Oellerich T, Herglotz J, Backert I, Kohrs N, Buscató EL, Wittmann SK, Salinas-Riester G, Bonig H, Karas M, Serve H, Proschak E, Lausen J. PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation. Nat Commun. 2014; 5: 3995. doi: 10.1038/ncomms4995
48. Gayatri S, Bedford MT. Readers of histone methylarginine marks. Biochim Biophys Acta. 2014; 1839: 702-710. doi: 10.1016/j.bbagrm.2014.02.015
49. Naik V, Leaf EM, Hu JH, Yang HY, Nguyen NB, Giachelli CM, Speer MY. Sources of cells that contribute to atherosclerotic intimal calcification: an in vivo genetic fate mapping study. Cardiovasc Res. 2012; 94: 545-554. doi: 10.1093/cvr/cvs126
50. Huang S, Li X, Yusufzai TM, Qiu Y, Felsenfeld G. USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier. Mol Cell Biol. 2007; 27: 7991-8002. doi: 10.1128/MCB.01326-07
51. Fan YM, Hernesniemi J, Oksala N, et al. Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque. Sci Rep. 2014; 4: 4650. doi: 10.1038/srep04650
52. Ito TK, Yokoyama M, Yoshida Y, Nojima A, Kassai H, Oishi K, Okada S, Kinoshita D, Kobayashi Y, Fruttiger M, Aiba A, Minamino T. A crucial role for CDC42 in senescence-associated inflammation and atherosclerosis. PLoS One. 2014; 9: e102186. doi: 10.1371/journal.pone.0102186
53. Suzuki W, Yamada A, Aizawa R, Suzuki D, Kassai H, Harada T, Nakayama M, Nagahama R, Maki K, Takeda S, Yamamoto M, Aiba A, Baba K, Kamijo R. Cdc42 is critical for cartilage development during endochondral ossification. Endocrinology. 2015; 156: 314-322. doi: 10.1210/en.2014-1032
54. Ito T, Yadav N, Lee J, Furumatsu T, Yamashita S, Yoshida K, Taniguchi N, Hashimoto M, Tsuchiya M, Ozaki T, Lotz M, Bedford MT, Asahara H. Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification. BMC Dev Biol. 2009; 9: 47. doi: 10.1186/1471-213X-9-47
55. Massari ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol. 2000; 20: 429-440
56. Bikkavilli RK, Malbon CC. Arginine methylation of G3BP1 in response to Wnt3a regulates β-catenin mRNA. J Cell Sci. 2011; 124: 2310-2320. doi: 10.1242/jcs.084046
57. Goel S, Chin EN, Fakhraldeen SA, Berry SM, Beebe DJ, Alexander CM. Both LRP5 and LRP6 receptors are required to respond to physiological Wnt ligands in mammary epithelial cells and fibroblasts. J Biol Chem. 2012; 287: 16454-16466. doi: 10.1074/jbc.M112.362137
58. New SE, Goettsch C, Aikawa M, Marchini JF, Shibasaki M, Yabusaki K, Libby P, Shanahan CM, Croce K, Aikawa E. Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ Res. 2013; 113: 72-77. doi: 10.1161/CIRCRESAHA.113.301036
59. Fisher EA, Miano JM. Don't judge books by their covers: vascular smooth muscle cells in arterial pathologies. Circulation. 2014; 129: 1545-1547. doi: 10.1161/CIRCULATIONAHA.114.009075
60. Swirski FK, Nahrendorf M. Do vascular smooth muscle cells differentiate to macrophages in atherosclerotic lesions?. Circ Res. 2014; 115: 605-606. doi: 10.1161/CIRCRESAHA.114.304925
61. Heath JM, Sun Y, Yuan K, Bradley WE, Litovsky S, Dell'Italia LJ, Chatham JC, Wu H, Chen Y. Activation of AKT by O-linked N-acetylglucosamine induces vascular calcification in diabetes mellitus. Circ Res. 2014; 114: 1094-1102. doi: 10.1161/CIRCRESAHA.114.302968
62. Zhang Y, Hassan MQ, Li ZY, Stein JL, Lian JB, van Wijnen AJ, Stein GS. Intricate gene regulatory networks of helix-loop-helix (HLH) proteins support regulation of bone-tissue related genes during osteoblast differentiation. J Cell Biochem. 2008; 105: 487-496. doi: 10.1002/jcb.21844