Genetic aspects of tissue-engineered constructs application in regenerative therapy in cardiology: analytical review

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Resumo

Traditional methods of treatment and prevention of cardiovascular disease (CVD) are not always effective, especially in severe myocardial injury. One of the promising areas for the treatment of cardiac pathologies is cell transplantation using tissue-engineered constructs from allogeneic stem cells, such as cell sheets. The success of cell therapy depends on the severity of local inflammatory reactions, angiogenesis activity, resistance of transplant cells to hypoxia and apoptosis, as well as on their production of extracellular matrix. Single nucleotide polymorphisms (SNPs) in genes involved in the processes associated with CDV can serve as markers of genetic dysfunction of these genes in the cardiovascular system and be used to predict the efficacy of the heart disease therapy based on tissue-engineered constructs. The review systematizes the information, allowing us to form a panel of such SNPs and analyze it. We identified seven genes at the intersection of pathways that are key to the survival of cellular constructs, VEGFA, TGFB1, FN1, IL6R, ITIH4, NRP1 and CDH13, and selected SNPs rs998584, rs8108632, rs1250259, rs6689306, rs77347777, rs75082222 and rs6565060, which are located in the regions of these genes and associated with CVD according to the Genome-Wide Association Study (GWAS). These polymorphisms may constitute a minimal panel to search for an association with the efficacy of cell therapy in heart disease.

Sobre autores

I. Kiselev

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Email: kiselev.ivan.1991@gmail.com
Moscow, 121552 Russia; Moscow, 117997 Russia

N. Matveeva

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Moscow, 121552 Russia; Moscow, 117997 Russia

I. Beloglazova

Chazov National Medical Research Center of Cardiology

Moscow, 121552 Russia

O. Kulakova

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Moscow, 121552 Russia; Moscow, 117997 Russia

O. Favorova

Chazov National Medical Research Center of Cardiology; Pirogov Russian National Research Medical University

Moscow, 121552 Russia; Moscow, 117997 Russia

Bibliografia

  1. Ziaeian B., Fonarow G.C. (2016) Epidemiology and aetiology of heart failure. Nat. Rev. Cardiol. 13, 368–378.
  2. Stougiannou T.M., Christodoulou K.C., Dima- rakis I., Mikroulis D., Karangelis D. (2024) To repair a broken heart: stem cells in ischemic heart disease. Curr. Issues Mol. Biol. 46, 2181–2208.
  3. Orlic D., Kajstura J., Chimenti S., Jakoniuk I., Anderson S.M., Li B., Pickel J., McKay R., Nadal-Ginard B., Bodine D.M., Leri A., Anversa P. (2001) Bone marrow cells regenerate infarcted myocardium. Nature. 410, 701–705.
  4. Nguyen P.K., Rhee J.-W., Wu J.C. (2016) Adult stem cell therapy and heart failure, 2000 to 2016: a systematic review. JAMA Cardiol. 1, 831–841.
  5. Tang X.-L., Li Q., Rokosh G., Sanganalmath S.K., Chen N., Ou Q., Stowers H., Hunt G., Bolli R. (2016) Long-term outcome of administration of c-kit(POS) cardiac progenitor cells after acute myocardial infarction: transplanted cells do not become cardiomyocytes, but structural and functional improvement and proliferation of endogenous cells persist for at least one year. Circ. Res. 118, 1091–1105.
  6. Парфенова Е.В., Дергилев К.В. (2023) Клеточная терапия в кардиологии: время надежд. Кардиологический вестник. 18(4), 7–18.
  7. Hare J.M., Fishman J.E., Gerstenblith G., DiFede Velazquez D.L., Zambrano J.P., Suncion V.Y., Tracy M., Ghersin E., Johnston P.V., Brinker J.A., Breton E., Davis-Sproul J., Schulman I.H., Byrnes J., Mendizabal A.M., Lowery M.H., Rouy D., Altman P., Wong Po Foo C., Ruiz P., Amador A., Da Silva J., McNiece I.K., Heldman A.W., George R., Lardo A. (2012) Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 308, 2369–2379.
  8. Nakatsuji N., Nakajima F., Tokunaga K. (2008) HLA-haplotype banking and iPS cells. Nat. Biotechnol. 26, 739–740.
  9. DeSandro A., Nagarajan U.M., Boss J.M. (1999) The bare lymphocyte syndrome: molecular clues to the transcriptional regulation of major histocompatibility complex class II genes. Am. J. Hum. Genet. 65, 279–286.
  10. Erlich H.A., Opelz G., Hansen J. (2001) HLA DNA typing and transplantation. Immunity. 14, 347–356.
  11. Shastry B.S. (2009) SNPs: impact on gene function and phenotype. Methods Mol. Biol. 578, 3–22.
  12. Di Nubila A., Dilella G., Simone R., Barbieri S.S. (2024) Vascular extracellular matrix in atherosclerosis. Int. J. Mol. Sci. 25, 12017.
  13. Abe H., Semba H., Takeda N. (2017) The roles of hypoxia signaling in the pathogenesis of cardiovascular diseases. J. Atheroscler. Thromb. 24, 884–894.
  14. Katz A.E., Ganesh S.K. (2023) Advancements in the genetics of spontaneous coronary artery dissection. Curr. Cardiol. Rep. 25, 1735–1743.
  15. Louzao-Martinez L., Vink A., Harakalova M., Asselbergs F.W., Verhaar M.C., Cheng C. (2016) Characteristic adaptations of the extracellular matrix in dilated cardiomyopathy. Int. J. Cardiol. 220, 634–646.
  16. González A., Fortuño M.A., Querejeta R., Ravassa S., López B., López N., Díez J. (2003) Cardiomyocyte apoptosis in hypertensive cardiomyopathy. Cardiovasc. Res. 59, 549–562.
  17. Verma A., Huffman J.E., Rodriguez A., Conery M., Liu M., Ho Y.L., Kim Y., Heise D.A., Guare L., Panickan V.A., Garcon H., Linares F., Costa L., Goethert I., Tipton R., Honerlaw J., Davies L., Whitbourne S., Cohen J., Posner D.C., Sangar R., Murray M., Wang X., Dochtermann D.R., Devineni P., Shi Y., Nandi T.N., Assimes T.L., Brunette C.A., Carroll R.J., Clifford R., Duvall S., Gelernter J., Hung A., Iyengar S.K., Joseph J., Kember R., Kranzler H., Kripke C.M., Levey D., Luoh S.W., Merritt V.C., Overstreet C., Deak J.D., Grant S.F.A., Polimanti R., Roussos P., Shakt G., Sun Y.V., Tsao N., Venkatesh S., Voloudakis G., Justice A., Begoli E., Ramoni R., Tourassi G., Pyarajan S., Tsao P., O’Donnell C.J., Muralidhar S., Moser J., Casas J.P., Bick A.G., Zhou W., Cai T., Voight B.F., Cho K., Gaziano J.M., Madduri R.K., Damrauer S., Liao K.P. (2024) Diversity and scale: genetic architecture of 2068 traits in the VA Million Veteran Program. Science. 385, eadj1182.
  18. Aragam K.G., Jiang T., Goel A., Kanoni S., Wolford B.N., Atri D.S., Weeks E.M., Wang M., Hindy G., Zhou W., Grace C., Roselli C., Marston N.A., Kamanu F.K., Surakka I., Venegas L.M., Sherliker P., Koyama S., Ishigaki K., Åsvold B.O., Brown M.R., Brumpton B., de Vries P.S., Giannakopoulou O., Giardoglou P., Gudbjartsson D.F., Güldener U., Haider S.M.I., Helgadottir A., Ibrahim M., Kastrati A., Kessler T., Kyriakou T., Konopka T., Li L., Ma L., Meitinger T., Mucha S., Munz M., Murgia F., Nielsen J.B., Nöthen M.M., Pang S., Reinberger T., Schnitzler G., Smedley D., Thorleifsson G., von Scheidt M., Ulirsch J.C.; Biobank Japan; EPIC–CVD; Arnar D.O., Burtt N.P., Costanzo M.C., Flannick J., Ito K., Jang D.K., Kamatani Y., Khera A.V., Komuro I., Kullo I.J., Lotta L.A., Nelson C.P., Roberts R., Thorgeirsson G., Thorsteinsdottir U., Webb T.R., Baras A., Björkegren J.L.M., Boerwinkle E., Dedoussis G., Holm H., Hveem K., Melander O., Morrison A.C., Orho-Melander M., Rallidis L.S., Ruusalepp A., Sabatine M.S., Stefansson K., Zalloua P., Ellinor P.T., Farrall M., Danesh J., Ruff C.T., Finucane H.K., Hopewell J.C., Clarke R., Gupta R.M., Erdmann J., Samani N.J., Schunkert H., Watkins H., Willer C.J., Deloukas P., Kathiresan S., Butterworth A.S.; CARDIoGRAMplusC4D Consortium. (2022) Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants. Nat. Genet. 54, 1803–1815.
  19. Zhou W., Nielsen J.B., Fritsche L.G., Dey R., Gabrielsen M.E., Wolford B.N., LeFaive J., VandeHaar P., Gagliano S.A., Gifford A., Bastarache L.A., Wei W.Q., Denny J.C., Lin M., Hveem K., Kang H.M., Abecasis G.R., Willer C.J., Lee S. (2018) Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat. Genet. 50, 1335–1341.
  20. van der Harst P., Verweij N. (2018) Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease. Circ. Res. 122, 433–443.
  21. Nelson C.P., Goel A., Butterworth A.S., Kanoni S., Webb T.R., Marouli E., Zeng L., Ntalla I., Lai F.Y., Hopewell J.C., Giannakopoulou O., Jiang T., Hamby S.E., Di Angelantonio E., Assimes T.L., Bottinger E.P., Chambers J.C., Clarke R., Palmer C.N.A., Cubbon R.M., Ellinor P., Ermel R., Evangelou E., Franks P.W., Grace C., Gu D., Hingorani A.D., Howson J.M.M., Ingelsson E., Kastrati A., Kessler T., Kyriakou T., Lehtimäki T., Lu X., Lu Y., März W., McPherson R., Metspalu A., Pujades-Rodriguez M., Ruusalepp A., Schadt E.E., Schmidt A.F., Sweeting M.J., Zalloua P.A., AlGhalayini K., Keavney B.D., Kooner J.S., Loos R.J.F., Patel R.S., Rutter M.K., Tomaszewski M., Tzoulaki I., Zeggini E., Erdmann J., Dedoussis G., Björkegren J.L.M.; EPIC–CVD Consortium; CARDIoGRAMplusC4D; UK Biobank CardioMetabolic Consortium CHD working group; Schunkert H., Farrall M., Danesh J., Samani N.J., Watkins H., Deloukas P. (2017) Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat. Genet. 49, 1385–1391.
  22. Klarin D., Zhu Q.M., Emdin C.A., Chaffin M., Horner S., McMillan B.J., Leed A., Weale M.E., Spencer C.C.A., Aguet F., Segrè A.V., Ardlie K.G., Khera A.V., Kaushik V.K., Natarajan P.; CARDIoGRAMplusC4D Consortium; Kathiresan S. (2017) Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to co- ronary artery disease. Nat. Genet. 49, 1392–1397.
  23. Matsunaga H., Ito K., Akiyama M., Takahashi A., Koyama S., Nomura S., Ieki H., Ozaki K., Onouchi Y., Sakaue S., Suna S., Ogishima S., Yamamoto M., Hozawa A., Satoh M., Sasaki M., Yamaji T., Sawada N., Iwasaki M., Tsugane S., Tanaka K., Arisawa K., Ikezaki H., Takashima N., Naito M., Wakai K., Tanaka H., Sakata Y., Morita H., Sakata Y., Matsuda K., Murakami Y., Akazawa H., Kubo M., Kamatani Y., Komuro I. (2020) Transethnic meta-analysis of genome-wide association sudies identifies three new loci and characterizes population-specific differences for coronary artery disease. Circ. Genom. Precis. Med. 13, e002670.
  24. Nikpay M., Goel A., Won H.H., Hall L.M., Willenborg C., Kanoni S., Saleheen D., Kyriakou T., Nelson C.P., Hopewell J.C., Webb T.R., Zeng L., Dehghan A., Alver M., Armasu S.M., Auro K., Bjonnes A., Chasman D.I., Chen S., Ford I., Franceschini N., Gieger C., Grace C., Gustafsson S., Huang J., Hwang S.J., Kim Y.K., Kleber M.E., Lau K.W., Lu X., Lu Y., Lyytikäinen L.P., Mihailov E., Morrison A.C., Pervjakova N., Qu L., Rose L.M., Salfati E., Saxena R., Scholz M., Smith A.V., Tikkanen E., Uitterlinden A., Yang X., Zhang W., Zhao W., de Andrade M., de Vries P.S., van Zuydam N.R., Anand S.S., Bertram L., Beutner F., Dedoussis G., Frossard P., Gauguier D., Goodall A.H., Gottesman O., Haber M., Han B.G., Huang J., Jalilzadeh S., Kessler T., König I.R., Lannfelt L., Lieb W., Lind L., Lindgren C.M., Lokki M.L., Magnusson P.K., Mallick N.H., Mehra N., Meitinger T., Memon F.U., Morris A.P., Nieminen M.S., Pedersen N.L., Peters A., Rallidis L.S., Rasheed A., Samuel M., Shah S.H., Sinisalo J., Stirrups K.E., Trompet S., Wang L., Zaman K.S., Ardissino D., Boerwinkle E., Borecki I.B., Bottinger E.P., Buring J.E., Chambers J.C., Collins R., Cupples L.A., Danesh J., Demuth I., Elosua R., Epstein S.E., Esko T., Feitosa M.F., Franco O.H., Franzosi M.G., Granger C.B., Gu D., Gudnason V., Hall A.S., Hamsten A., Harris T.B., Hazen S.L., Hengstenberg C., Hofman A., Ingelsson E., Iribarren C., Jukema J.W., Karhunen P.J., Kim B.J., Kooner J.S., Kullo I.J., Lehtimäki T., Loos R.J.F., Melander O., Metspalu A., März W., Palmer C.N., Perola M., Quertermous T., Rader D.J., Ridker P.M., Ripatti S., Roberts R., Salomaa V., Sanghera D.K., Schwartz S.M., Seedorf U., Stewart A.F., Stott D.J., Thiery J., Zalloua P.A., O’Donnell C.J., Reilly M.P., Assimes T.L., Thompson J.R., Erdmann J., Clarke R., Watkins H., Kathiresan S., McPherson R., Deloukas P., Schunkert H., Samani N.J., Farrall M. (2015) A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery disease. Nat. Genet. 47, 1121–1130.
  25. Adlam D., Berrandou T.E., Georges A., Nelson C.P., Giannoulatou E., Henry J., Ma L., Blencowe M., Turley T.N., Yang M.L., Chopade S., Finan C., Braund P.S., Sadeg-Sayoud I., Iismaa S.E., Kosel M.L., Zhou X., Hamby S.E., Cheng J., Liu L., Tarr I., Muller D.W.M., d’Escamard V., King A., Brunham L.R., Baranowska-Clarke A.A., Debette S., Amouyel P., Olin J.W., Patil S., Hesselson S.E., Junday K., Kanoni S., Aragam K.G., Butterworth A.S.; CARDIoGRAMPlusC4D; MEGASTROKE; International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group; Tweet M.S., Gulati R., Combaret N.; DISCO register; Kadian-Dodov D., Kalman J.M., Fatkin D., Hingorani A.D., Saw J., Webb T.R., Hayes S.N., Yang X., Ganesh S.K., Olson T.M., Kovacic J.C., Graham R.M., Samani N.J., Bouatia-Naji N. (2023) Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation. Nat. Genet. 55, 964–972.
  26. Schunkert H., König I.R., Kathiresan S., Reilly M.P., Assimes T.L., Holm H., Preuss M., Stewart A.F., Barbalic M., Gieger C., Absher D., Aherrahrou Z., Allayee H., Altshuler D., Anand S.S., Andersen K., Anderson J.L., Ardissino D., Ball S.G., Balmforth A.J., Barnes T.A., Becker D.M., Becker L.C., Berger K., Bis J.C., Boekholdt S.M., Boerwinkle E., Braund P.S., Brown M.J., Burnett M.S., Buysschaert I.; Cardiogenics; Carlquist J.F., Chen L., Cichon S., Codd V., Davies R.W., Dedoussis G., Dehghan A., Demissie S., Devaney J.M., Diemert P., Do R., Doering A., Eifert S., Mokhtari N.E., Ellis S.G., Elosua R., Engert J.C., Epstein S.E., de Faire U., Fischer M., Folsom A.R., Freyer J., Gigante B., Girelli D., Gretarsdottir S., Gudnason V., Gulcher J.R., Halperin E., Hammond N., Hazen S.L., Hofman A., Horne B.D., Illig T., Iribarren C., Jones G.T., Jukema J.W., Kaiser M.A., Kaplan L.M., Kastelein J.J., Khaw K.T., Knowles J.W., Kolovou G., Kong A., Laaksonen R., Lambrechts D., Leander K., Lettre G., Li M., Lieb W., Loley C., Lotery A.J., Mannucci P.M., Maouche S., Martinelli N., McKeown P.P., Meisinger C., Meitinger T., Melander O., Merlini P.A., Mooser V., Morgan T., Mühleisen T.W., Muhlestein J.B., Münzel T., Musunuru K., Nahrstaedt J., Nelson C.P., Nöthen M.M., Olivieri O., Patel R.S., Patterson C.C., Peters A., Peyvandi F., Qu L., Quyyumi A.A., Rader D.J., Rallidis L.S., Rice C., Rosendaal F.R., Rubin D., Salomaa V., Sampietro M.L., Sandhu M.S., Schadt E., Schäfer A., Schillert A., Schreiber S., Schrezenmeir J., Schwartz S.M., Siscovick D.S., Sivananthan M., Sivapalaratnam S., Smith A., Smith T.B., Snoep J.D., Soranzo N., Spertus J.A., Stark K., Stirrups K., Stoll M., Tang W.H., Tennstedt S., Thorgeirsson G., Thorleifsson G., Tomaszewski M., Uitterlinden A.G., van Rij A.M., Voight B.F., Wareham N.J., Wells G.A., Wichmann H.E., Wild P.S., Willenborg C., Witteman J.C., Wright B.J., Ye S., Zeller T., Ziegler A., Cambien F., Goodall A.H., Cupples L.A., Quertermous T., März W., Hengstenberg C., Blankenberg S., Ouwehand W.H., Hall A.S., Deloukas P., Thompson J.R., Stefansson K., Roberts R., Thorsteinsdottir U., O’Donnell C.J., McPherson R., Erdmann J.; CARDIoGRAM Consortium; Samani N.J. (2011) Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 43, 333–338.
  27. Tcheandjieu C., Zhu X., Hilliard A.T., Clarke S.L., Napolioni V., Ma S., Lee K.M., Fang H., Chen F., Lu Y., Tsao N.L., Raghavan S., Koyama S., Gorman B.R., Vujkovic M., Klarin D., Levin M.G., Sinnott-Armstrong N., Wojcik G.L., Plomondon M.E., Maddox T.M., Waldo S.W., Bick A.G., Pyarajan S., Huang J., Song R., Ho Y.L., Buyske S., Kooperberg C., Haessler J., Loos R.J.F., Do R., Verbanck M., Chaudhary K., North K.E., Avery C.L., Graff M., Haiman C.A., Le Marchand L., Wilkens L.R., Bis J.C., Leonard H., Shen B., Lange L.A., Giri A., Dikilitas O., Kullo I.J., Stanaway I.B., Jarvik G.P., Gordon A.S., Hebbring S., Namjou B., Kaufman K.M., Ito K., Ishigaki K., Kamatani Y., Verma S.S., Ritchie M.D., Kember R.L., Baras A., Lotta L.A.; Regeneron Genetics Center; CARDIoGRAMplusC4D Consortium; Biobank Japan; Million Veteran Program; Kathiresan S., Hauser E.R., Miller D.R., Lee J.S., Saleheen D., Reaven P.D., Cho K., Gaziano J.M., Natarajan P., Huffman J.E., Voight B.F., Rader D.J., Chang K.M., Lynch J.A., Damrauer S.M., Wilson P.W.F., Tang H., Sun Y.V., Tsao P.S., O’Donnell C.J., Assimes T.L. (2022) Large-scale genome-wide association study of coronary artery disease in genetically diverse populations. Nat. Med. 28, 1679–1692.
  28. Harper A.R., Goel A., Grace C., Thomson K.L., Petersen S.E., Xu X., Waring A., Ormondroyd E., Kramer C.M., Ho C.Y., Neubauer S.; HCMR Investigators; Tadros R., Ware J.S., Bezzina C.R., Farrall M., Watkins H. (2021) Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity. Nat. Genet. 53, 135–142.
  29. Tadros R., Zheng S.L., Grace C., Jordà P., Francis C., West D.M., Jurgens S.J., Thomson K.L., Harper A.R., Ormondroyd E., Xu X., Theotokis P.I., Buchan R.J., McGurk K.A., Mazzarotto F., Boschi B., Pelo E., Lee M., Noseda M., Varnava A., Vermeer A.M.C., Walsh R., Amin A.S., van Slegtenhorst M.A., Roslin N.M., Strug L.J., Salvi E., Lanzani C., de Marvao A.; Hypergenes InterOmics Collaborators; Roberts J.D., Tremblay-Gravel M., Giraldeau G., Cadrin-Tourigny J., L’Allier P.L., Garceau P., Talajic M., Gagliano Taliun S.A., Pinto Y.M., Rakowski H., Pantazis A., Bai W., Baksi J., Halliday B.P., Prasad S.K., Barton P.J.R., O’Regan D.P., Cook S.A., de Boer R.A., Christiaans I., Michels M., Kramer C.M., Ho C.Y., Neubauer S.; HCMR Investigators; Matthews P.M., Wilde A.A.M., Tardif J.C., Olivotto I., Adler A., Goel A., Ware J.S., Bezzina C.R., Watkins H. (2025) Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy. Nat. Genet. 57, 530–538.
  30. Hartiala J.A., Han Y., Jia Q., Hilser J.R., Huang P., Gukasyan J., Schwartzman W.S., Cai Z., Biswas S., Trégouët D.A., Smith N.L.; INVENT Consortium; CHARGE Consortium Hemostasis Working Group; GENIUS-CHD Consortium; Seldin M., Pan C., Mehrabian M., Lusis A.J., Bazeley P., Sun Y.V., Liu C., Quyyumi A.A., Scholz M., Thiery J., Delgado G.E., Kleber M.E., März W., Howe L.J., Asselbergs F.W., van Vugt M., Vlachojannis G.J., Patel R.S., Lyytikäinen L.P., Kähönen M., Lehtimäki T., Nieminen T.V.M., Kuukasjärvi P., Laurikka J.O., Chang X., Heng C.K., Jiang R., Kraus W.E., Hauser E.R., Ferguson J.F., Reilly M.P., Ito K., Koyama S., Kamatani Y., Komuro I.; Biobank Japan; Stolze L.K., Romanoski C.E., Khan M.D., Turner A.W., Miller C.L., Aherrahrou R., Civelek M., Ma L., Björkegren J.L.M., Kumar S.R., Tang W.H.W., Hazen S.L., Allayee H. (2021) Genome-wide analysis identifies novel susceptibility loci for myocardial infarction. Eur. Heart J. 42, 919–933.
  31. Sakaue S., Kanai M., Tanigawa Y., Karjalainen J., Kurki M., Koshiba S., Narita A., Konuma T., Yamamoto K., Akiyama M., Ishigaki K., Suzuki A., Suzuki K., Obara W., Yamaji K., Takahashi K., Asai S., Takahashi Y., Suzuki T., Shinozaki N., Yamaguchi H., Minami S., Murayama S., Yoshimori K., Nagayama S., Obata D., Higashiyama M., Masumoto A., Koretsune Y.; FinnGen; Ito K., Terao C., Yamauchi T., Komuro I., Kadowaki T., Tamiya G., Yamamoto M., Nakamura Y., Kubo M., Murakami Y., Yamamoto K., Kamatani Y., Palotie A., Rivas M.A., Daly M.J., Matsuda K., Okada Y. (2021) A cross-population atlas of genetic associations for 220 human phenotypes. Nat. Genet. 53, 1415–1424.
  32. Shah S., Henry A., Roselli C., Lin H., Sveinbjörnsson G., Fatemifar G., Hedman Å.K., Wilk J.B., Morley M.P., Chaffin M.D., Helgadottir A., Verweij N., Dehghan A., Almgren P., Andersson C., Aragam K.G., Ärnlöv J., Backman J.D., Biggs M.L., Bloom H.L., Brandimarto J., Brown M.R., Buckbinder L., Carey D.J., Chasman D.I., Chen X., Chen X., Chung J., Chutkow W., Cook J.P., Delgado G.E., Denaxas S., Doney A.S., Dörr M., Dudley S.C., Dunn M.E., Engström G., Esko T., Felix S.B., Finan C., Ford I., Ghanbari M., Ghasemi S., Giedraitis V., Giulianini F., Gottdiener J.S., Gross S., Guðbjartsson D.F., Gutmann R., Haggerty C.M., van der Harst P., Hyde C.L., Ingelsson E., Jukema J.W., Kavousi M., Khaw K.T., Kleber M.E., Køber L., Koekemoer A., Langenberg C., Lind L., Lindgren C.M., London B., Lotta L.A., Lovering R.C., Luan J., Magnusson P., Mahajan A., Margulies K.B., März W., Melander O., Mordi I.R., Morgan T., Morris A.D., Morris A.P., Morrison A.C., Nagle M.W., Nelson C.P., Niessner A., Niiranen T., O’Donoghue M.L., Owens A.T., Palmer C.N.A., Parry H.M., Perola M., Portilla-Fernandez E., Psaty B.M.; Regeneron Genetics Center; Rice K.M., Ridker P.M., Romaine S.P.R., Rotter J.I., Salo P., Salomaa V., van Setten J., Shalaby A.A., Smelser D.T., Smith N.L., Stender S., Stott D.J., Svensson P., Tammesoo M.L., Taylor K.D., Teder-Laving M., Teumer A., Thorgeirsson G., Thorsteinsdottir U., Torp-Pedersen C., Trompet S., Tyl B., Uitterlinden A.G., Veluchamy A., Völker U., Voors A.A., Wang X., Wareham N.J., Waterworth D., Weeke P.E., Weiss R., Wiggins K.L., Xing H., Yerges-Armstrong L.M., Yu B., Zannad F., Zhao J.H., Hemingway H., Samani N.J., McMurray J.J.V., Yang J., Visscher P.M., Newton-Cheh C., Malarstig A., Holm H., Lubitz S.A., Sattar N., Holmes M.V., Cappola T.P., Asselbergs F.W., Hingorani A.D., Kuchenbaecker K., Ellinor P.T., Lang C.C., Stefansson K., Smith J.G., Vasan R.S., Swerdlow D.I., Lumbers R.T. (2020) Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat. Commun. 11, 163.
  33. Levin M.G., Tsao N.L., Singhal P., Liu C., Vy H.M.T., Paranjpe I., Backman J.D., Bellomo T.R., Bone W.P., Biddinger K.J., Hui Q., Dikilitas O., Satterfield B.A., Yang Y., Morley M.P., Bradford Y., Burke M., Reza N., Charest B.; Regeneron Genetics Center; Judy R.L., Puckelwartz M.J., Hakonarson H., Khan A., Kottyan L.C., Kullo I., Luo Y., McNally E.M., Rasmussen-Torvik L.J., Day S.M., Do R., Phillips L.S., Ellinor P.T., Nadkarni G.N., Ritchie M.D., Arany Z., Cappola T.P., Margulies K.B., Aragam K.G., Haggerty C.M., Joseph J., Sun Y.V., Voight B.F., Damrauer S.M. (2022) Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure. Nat. Commun. 13, 6914.
  34. Garnier S., Harakalova M., Weiss S., Mokry M., Regitz-Zagrosek V., Hengstenberg C., Cappola T.P., Isnard R., Arbustini E., Cook S.A., van Setten J., Calis J.J.A., Hakonarson H., Morley M.P., Stark K., Prasad S.K., Li J., O’Regan D.P., Grasso M., Müller- Nurasyid M., Meitinger T., Empana J.P., Strauch K., Waldenberger M., Marguiles K.B., Seidman C.E., Kararigas G., Meder B., Haas J., Boutouyrie P., Lacolley P., Jouven X., Erdmann J., Blankenberg S., Wichter T., Ruppert V., Tavazzi L., Dubourg O., Roizes G., Dorent R., de Groote P., Fauchier L., Trochu J.N., Aupetit J.F., Bilinska Z.T., Germain M., Völker U., Hemerich D., Raji I., Bacq-Daian D., Proust C., Remior P., Gomez-Bueno M., Lehnert K., Maas R., Olaso R., Saripella G.V., Felix S.B., McGinn S., Duboscq-Bidot L., van Mil A., Besse C., Fontaine V., Blanché H., Ader F., Keating B., Curjol A., Boland A., Komajda M., Cambien F., Deleuze J.F., Dörr M., Asselbergs F.W., Villard E., Trégouët D.A., Charron P. (2021) Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23. Eur. Heart J. 42, 2000–2011.
  35. Kavousi M., Bos M.M., Barnes H.J., Lino Cardenas C.L., Wong D., Lu H., Hodonsky C.J., Landsmeer L.P.L., Turner A.W., Kho M., Hasbani N.R., de Vries P.S., Bowden D.W., Chopade S., Deelen J., Benavente E.D., Guo X., Hofer E., Hwang S.J., Lutz S.M., Lyytikäinen L.P., Slenders L., Smith A.V., Stanislawski M.A., van Setten J., Wong Q., Yanek L.R., Becker D.M., Bee- kman M., Budoff M.J., Feitosa M.F., Finan C., Hilliard A.T., Kardia S.L.R., Kovacic J.C., Kral B.G., Langefeld C.D., Launer L.J., Malik S., Hoesein F.A.A.M., Mokry M., Schmidt R., Smith J.A., Taylor K.D., Terry J.G., van der Grond J., van Meurs J., Vliegenthart R., Xu J., Young K.A., Zilhão N.R., Zweiker R., Assimes T.L., Becker L.C., Bos D., Carr J.J., Cupples L.A., de Kleijn D.P.V., de Winther M., den Ruijter H.M., Fornage M., Freedman B.I., Gudnason V., Hingorani A.D., Hokanson J.E., Ikram M.A., Išgum I., Jacobs D.R.Jr., Kähönen M., Lange L.A., Lehtimäki T., Pasterkamp G., Raitakari O.T., Schmidt H., Slagboom P.E., Uitterlinden A.G., Vernooij M.W., Bis J.C., Franceschini N., Psaty B.M., Post W.S., Rotter J.I., Björkegren J.L.M., O’Donnell C.J., Bielak L.F., Peyser P.A., Malhotra R., van der Laan S.W., Miller C.L. (2023) Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification. Nat. Genet. 55, 1651–1664.
  36. Hutchings H., Ortega N., Plouët J. (2003) Extracellular matrix-bound vascular endothelial growth factor promotes endothelial cell adhesion, migration, and survival through integrin ligation. FASEB J. 17, 1520–1522.
  37. Huang L.O., Rauch A., Mazzaferro E., Preuss M., Carobbio S., Bayrak C.S., Chami N., Wang Z., Schick U.M., Yang N., Itan Y., Vidal-Puig A., den Hoed M., Mandrup S., Kilpeläinen T.O., Loos R.J.F. (2021) Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. Nat. Metab. 3, 228–243.
  38. Lee W.J., Lim J.E., Kang J.O., Ha T.W., Jung H.U., Kim D.J., Baek E.J., Kim H.K., Chung J.Y., Oh B. (2022) Smoking-interaction loci affect obesity traits: a gene-smoking stratified meta-analysis of 545,131 Europeans. Lifestyle Genom. 15, 87–97.
  39. Dastani Z., Hivert M.F., Timpson N., Perry J.R., Yuan X., Scott R.A., Henneman P., Heid I.M., Kizer J.R., Lyytikäinen L.P., Fuchsberger C., Tanaka T., Morris A.P., Small K., Isaacs A., Beekman M., Coassin S., Lohman K., Qi L., Kanoni S., Pankow J.S., Uh H.W., Wu Y., Bidulescu A., Rasmussen-Torvik L.J., Greenwood C.M., Ladouceur M., Grimsby J., Manning A.K., Liu C.T., Kooner J., Mooser V.E., Vollenweider P., Kapur K.A., Chambers J., Wareham N.J., Langenberg C., Frants R., Willems-Vandijk K., Oostra B.A., Willems S.M., Lamina C., Winkler T.W., Psaty B.M., Tracy R.P., Brody J., Chen I., Viikari J., Kähönen M., Pramstaller P.P., Evans D.M., St Pourcain B., Sattar N., Wood A.R., Bandinelli S., Carlson O.D., Egan J.M., Böhringer S., van Heemst D., Kedenko L., Kristiansson K., Nuotio M.L., Loo B.M., Harris T., Garcia M., Kanaya A., Haun M., Klopp N., Wichmann H.E., Deloukas P., Katsareli E., Couper D.J., Duncan B.B., Kloppenburg M., Adair L.S., Borja J.B.; DIAGRAM+ Consortium; MAGIC Consortium; GLGC Investigators; MuTHER Consortium; Wilson J.G., Musani S., Guo X., Johnson T., Semple R., Teslovich T.M., Allison M.A., Redline S., Buxbaum S.G., Mohlke K.L., Meulenbelt I., Ballantyne C.M., Dedoussis G.V., Hu F.B., Liu Y., Paulweber B., Spector T.D., Slagboom P.E., Ferrucci L., Jula A., Perola M., Raitakari O., Florez J.C., Salomaa V., Eriksson J.G., Frayling T.M., Hicks A.A., Lehtimäki T., Smith G.D., Siscovick D.S., Kronenberg F., van Duijn C., Loos R.J., Waterworth D.M., Meigs J.B., Dupuis J., Richards J.B., Voight B.F., Scott L.J., Steinthorsdottir V., Dina C., Welch R.P., Zeggini E., Huth C., Aulchenko Y.S., Thorleifsson G., McCulloch L.J., Ferreira T., Grallert H., Amin N., Wu G., Willer C.J., Raychaudhuri S., McCarroll S.A., Hofmann O.M., Segrè A.V., van Hoek M., Navarro P., Ardlie K., Balkau B., Benediktsson R., Bennett A.J., Blagieva R., Boerwinkle E., Bonnycastle L.L., Boström K.B., Bravenboer B., Bumpstead S., Burtt N.P., Charpentier G., Chines P.S., Cornelis M., Crawford G., Doney A.S., Elliott K.S., Elliott A.L., Erdos M.R., Fox C.S., Franklin C.S., Ganser M., Gieger C., Grarup N., Green T., Griffin S., Groves C.J., Guiducci C., Hadjadj S., Hasanali N., Herder C., Isomaa B., Jackson A.U., Johnson P.R., Jørgensen T., Kao W.H., Kong A., Kraft P., Kuusisto J., Lauritzen T., Li M., Lieverse A., Lindgren C. M., Lyssenko V., Marre M., Meitinger T., Midthjell K., Morken M.A., Narisu N., Nilsson P., Owen K.R., Payne F., Petersen A.K., Platou C., Proença C., Prokopenko I., Rathmann W., Rayner N.W., Robertson N.R., Rocheleau G., Roden M., Sampson M.J., Saxena R., Shields B.M., Shrader P., Sigurdsson G., Sparsø T., Strassburger K., Stringham H.M., Sun Q., Swift A.J., Thorand B., Tichet J., Tuomi T., van Dam R.M., van Haeften T.W., van Herpt T., van Vliet-Ostaptchouk J.V., Walters G.B., Weedon M.N., Wijmenga C., Witteman J., Bergman R.N., Cauchi S., Collins F.S., Gloyn A.L., Gyllensten U., Hansen T., Hide W.A., Hitman G.A., Hofman A., Hunter D.J., Hveem K., Laakso M., Morris A.D., Palmer C.N., Rudan I., Sijbrands E., Stein L.D., Tuomilehto J., Uitterlinden A., Walker M., Watanabe R.M., Abecasis G.R., Boehm B.O., Campbell H., Daly M.J., Hattersley A.T., Pedersen O., Barroso I., Groop L., Sladek R., Thorsteinsdottir U., Wilson J.F., Illig T., Froguel P., van Duijn C.M., Stefansson K., Altshuler D., Boehnke M., McCarthy M.I., Soranzo N., Wheeler E., Glazer N.L., Bouatia-Naji N., Mägi R., Randall J., Elliott P., Rybin D., Dehghan A., Hottenga J.J., Song K., Goel A., Lajunen T., Doney A., Cavalcanti-Proença C., Kumari M., Timpson N.J., Zabena C., Ingelsson E., An P., O’Connell J., Luan J., Elliott A., McCarroll S.A., Roccasecca R.M., Pattou F., Sethupathy P., Ariyurek Y., Barter P., Beilby J.P., Ben-Shlomo Y., Bergmann S., Bochud M., Bonnefond A., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead S.J., Chen Y.D., Chines P., Clarke R., Coin L.J., Cooper M.N., Crisponi L., Day I.N., de Geus E.J., Delplanque J., Fedson A.C., Fischer-Rosinsky A., Forouhi N.G., Franzosi M.G., Galan P., Goodarzi M.O., Graessler J., Grundy S., Gwilliam R., Hallmans G., Hammond N., Han X., Hartikainen A.L., Hayward C., Heath S.C., Hercberg S., Hillman D.R., Hingorani A.D., Hui J., Hung J., Kaakinen M., Kaprio J., Kesaniemi Y.A., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik K.O., Lathrop G.M., Lawlor D.A., Le Bacquer O., Lecoeur C., Li Y., Mahley R., Mangino M., Martínez-Larrad M.T., McAteer J.B., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell B.D., Mukherjee S., Naitza S., Neville M.J., Orrù M., Pakyz R., Paolisso G., Pattaro C., Pearson D., Peden J.F., Pedersen N.L., Pfeiffer A.F., Pichler I., Polasek O., Posthuma D., Potter S.C., Pouta A., Province M.A., Rayner N.W., Rice K., Ripatti S., Rivadeneira F., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer A.A., Scheet P., Seedorf U., Sharp S.J., Shields B., Sigurðsson G., Sijbrands E.J., Silveira A., Simpson L., Singleton A., Smith N.L., Sovio U., Swift A., Syddall H., Syvänen A.C., Tönjes A., Uitterlinden A.G., van Dijk K.W., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner P.J., Walley A., Ward K.L., Watkins H., Wild S.H., Willemsen G., Witteman J.C., Yarnell J.W., Zelenika D., Zethelius B., Zhai G., Zhao J.H., Zillikens M.C.; DIAGRAM Consortium; GIANT Consortium; Global B Pgen Consortium; Borecki I.B., Meneton P., Magnusson P.K., Nathan D.M., Williams G.H., Silander K., Bornstein S.R., Schwarz P., Spranger J., Karpe F., Shuldiner A.R., Cooper C., Serrano-Ríos M., Lind L., Palmer L.J., Hu F.B. 1st, Franks P.W., Ebrahim S., Marmot M., Kao W.H., Pramstaller P.P., Wright A.F., Stumvoll M., Hamsten A.; Procardis Consortium; Buchanan T.A., Valle T.T., Rotter J.I., Penninx B.W., Boomsma D.I., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin M.R., Peltonen L., Mooser V., Sladek R.; MAGIC investigators; GLGC Consortium; Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Chasman D.I., Johansen C.T., Fouchier S.W., Peloso G.M., Barbalic M., Ricketts S.L., Bis J.C., Feitosa M.F., Orho-Melander M., Melander O., Li X., Li M., Cho Y.S., Go M.J., Kim Y.J., Lee J.Y., Park T., Kim K., Sim X., Ong R.T., Croteau-Chonka D.C., Lange L.A., Smith J.D., Ziegler A., Zhang W., Zee R.Y., Whitfield J.B., Thompson J.R., Surakka I., Spector T.D., Smit J.H., Sinisalo J., Scott J., Saharinen J., Sabatti C., Rose L.M., Roberts R., Rieder M., Parker A.N., Pare G., O’Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W., McArdle W., Masson D., Martin N.G., Marroni F., Lucas G., Luben R., Lokki M.L., Lettre G., Launer L.J., Lakatta E.G., Laaksonen R., Kyvik K.O., König I.R., Khaw K.T., Kaplan L.M., Johansson Å., Janssens A.C., Igl W., Hovingh G.K., Hengstenberg C., Havulinna A.S., Hastie N.D., Harris T.B., Haritunians T., Hall A.S., Groop L.C., Gonzalez E., Freimer N.B., Erdmann J., Ejebe K.G., Döring A., Dominiczak A.F., Demissie S., Deloukas P., de Faire U., Crawford G., Chen Y.D., Caulfield M.J., Boekholdt S.M., Assimes T.L., Quertermous T., Seielstad M., Wong T.Y., Tai E.S., Feranil A.B., Kuzawa C.W., Taylor H.A.Jr., Gabriel S.B., Holm H., Gudnason V., Krauss R.M., Ordovas J.M., Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J., Schadt E.E., Strachan D.P., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A., Sandhu M.S., Ridker P.M., Rader D.J., Kathiresan S. (2012) Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 8, e1002607.
  40. Richardson L., Wilcockson S.G., Guglielmi L., Hill C.S. (2023) Context-dependent TGFβ family signalling in cell fate regulation. Nat. Rev. Mol. Cell Biol. 24, 876–894.
  41. Zarkasi K.A., Abdullah N., Abdul Murad N.A., Ahmad N., Jamal R. (2022) Genetic factors for coronary heart disease and their mechanisms: a meta-analysis and comprehensive review of common variants from genome-wide association studies. Diagnostics (Basel). 12, 2561.
  42. Zollinger A.J., Smith M.L. (2017) Fibronectin, the extracellular glue. Matrix Biol. 60–61, 27–37.
  43. Soubeyrand S., Lau P., Nikpay M., Dang A.-T., McPherson R. (2022) Common polymorphism that protects from cardiovascular disease increases fibronectin processing and secretion. Circ. Genom. Precis Med. 15, e003428.
  44. Parker M.W., Guo H.-F., Li X., Linkugel A.D., Vander Kooi C.W. (2012) Function of members of the neuropilin family as essential pleiotropic cell surface receptors. Biochemistry. 51, 9437–9446.
  45. Chikh A., Raimondi C. (2024) Endothelial Neuropilin-1: a multifaced signal transducer with an emerging role in inflammation and atherosclerosis beyond angiogenesis. Biochem. Soc. Trans. 52, 137–150.
  46. Spencer S., Köstel Bal S., Egner W., Lango Allen H., Raza S.I., Ma C.A., Gürel M., Zhang Y., Sun G., Sabroe R.A., Greene D., Rae W., Shahin T., Kania K., Ardy R.C., Thian M., Staples E., Pecchia-Bekkum A., Worrall W.P.M., Stephens J., Brown M., Tuna S., York M., Shackley F., Kerrin D., Sargur R., Condliffe A., Tipu H.N., Kuehn H.S., Rosenzweig S.D., Turro E., Tavaré S., Thrasher A.J., Jodrell D.I., Smith K.G.C., Boztug K., Milner J.D., Thaventhiran J.E.D. (2019) Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J. Exp. Med. 216, 1986–1998.
  47. Garbers C., Thaiss W., Jones G.W., Waetzig G.H., Lorenzen I., Guilhot F., Lissilaa R., Ferlin W.G., Grötzinger J., Jones S.A., Rose-John S., Scheller J. (2011) Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J. Biol. Chem. 286, 42959–42970.
  48. Rosa M., Chignon A., Li Z., Boulanger M.-C., Arsenault B.J., Bossé Y., Thériault S., Mathieu P. (2019) A Mendelian randomization study of IL6 signaling in cardiovascular diseases, immune-related disorders and longevity. NPJ Genom. Med. 4, 23.
  49. Pihl R., Jensen R.K., Poulsen E.C., Jensen L., Hansen A.G., Thøgersen I.B., Dobó J., Gál P., Andersen G.R., Enghild J.J., Thiel S. (2021) ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism. Sci. Adv. 7, eaba7381.
  50. Huo Y., Lai Y., Feng Q., Wang Q., Li J. (2022) Serum ITIH4 in coronary heart disease: a potential anti-inflammatory biomarker related to stenosis degree and risk of major adverse cardiovascular events. Biomark. Med. 16, 1279–1288.
  51. Ravindran A., Holappa L., Niskanen H., Skovo- rodkin I., Kaisto S., Beter M., Kiema M., Selvarajan I., Nurminen V., Aavik E., Aherrahrou R., Pasonen-Seppänen S., Fortino V., Laakkonen J.P., Ylä-Herttuala S., Vainio S., Örd T., Kaikkonen M.U. (2024) Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis. Cardiovasc. Res. 120, 869–882.
  52. Andreeva A.V., Han J., Kutuzov M.A., Profirovic J., Tkachuk V.A., Voyno-Yasenetskaya T.A. (2010) T-cadherin modulates endothelial barrier function. J. Cell. Physiol. 223, 94–102.
  53. Rubina K.A., Semina E.V., Kalinina N.I., Sysoeva V.Y., Balatskiy A.V., Tkachuk V.A. (2021) Revisiting the multiple roles of T-cadherin in health and disease. Eur. J. Cell Biol. 100, 151183.
  54. Pfaff D., Philippova M., Kyriakakis E., Maslova K., Rupp K., Buechner S.A., Iezzi G., Spagnoli G.C., Erne P., Resink T.J. (2011) Paradoxical effects of T-cadherin on squamous cell carcinoma: up- and down-regulation increase xenograft growth by distinct mechanisms. J. Pathol. 225, 512–524.
  55. Philippova M., Banfi A., Ivanov D., Gianni-Barrera R., Allenspach R., Erne P., Resink T. (2006) Atypical GPI-anchored T-cadherin stimulates angiogenesis in vitro and in vivo. Arterioscler. Thromb. Vasc. Biol. 26, 2222–2230.
  56. Shao Y., Li W., Zhang L., Xue B., Chen Y., Zhang Z., Wang D., Wu B. (2022) CDH13 is a prognostic biomarker and a potential therapeutic target for patients with clear cell renal cell carcinoma. Am. J. Cancer Res. 12, 4520‒4544.

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