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Basic Research in Cardiology

, 113:38 | Cite as

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction

  • Edward D. Coverstone
  • Richard G. Bach
  • LiShiun Chen
  • Laura J. Bierut
  • Allie Y. Li
  • Petra A. Lenzini
  • Heidi C. O’Neill
  • John A. Spertus
  • Carmen C. Sucharov
  • Jerry A. Stitzel
  • Joel D. Schilling
  • Sharon Cresci
Original Contribution

Abstract

The CHRNA5 gene encodes a neurotransmitter receptor subunit involved in multiple processes, including cholinergic autonomic nerve activity and inflammation. Common variants in CHRNA5 have been linked with atherosclerotic cardiovascular disease. Association of variation in CHRNA5 and specific haplotypes with cardiovascular outcomes has not been described. The aim of this study was to examine the association of CHRNA5 haplotypes with gene expression and mortality among patients with acute myocardial infarction (AMI) and explore potential mechanisms of this association. Patients (N = 2054) hospitalized with AMI were genotyped for two common variants in CHRNA5. Proportional hazard models were used to estimate independent association of CHRNA5 haplotype with 1-year mortality. Both individual variants were associated with mortality (p = 0.0096 and 0.0004, respectively) and were in tight LD (D′ = 0.99). One haplotype, HAP3, was associated with decreased mortality one year after AMI (adjusted HR = 0.42, 95% CI 0.26, 0.68; p = 0.0004). This association was validated in an independent cohort (N = 637) of post-MI patients (adjusted HR = 0.23, 95% CI 0.07, 0.79; p = 0.019). Differences in CHRNA5 expression by haplotype were investigated in human heart samples (n = 28). Compared with non-carriers, HAP3 carriers had threefold lower cardiac CHRNA5 mRNA expression (p = 0.023). Circulating levels of the inflammatory marker hsCRP were significantly lower in HAP3 carriers versus non-carriers (3.43 ± 4.2 versus 3.91 ± 5.1; p = 0.0379). Activation of the inflammasome, an important inflammatory complex involved in cardiovascular disease that is necessary for release of the pro-inflammatory cytokine IL-1 β, was assessed in bone marrow-derived macrophages (BMDM) from CHRNA5 knockout mice and wild-type controls. In BMDM from CHRNA5 knockout mice, IL-1β secretion was reduced by 50% compared to wild-type controls (p = 0.004). Therefore, a common haplotype of CHRNA5 that results in reduced cardiac expression of CHRNA5 and attenuated macrophage inflammasome activation is associated with lower mortality after AMI. These results implicate CHRNA5 and the cholinergic anti-inflammatory pathway in survival following AMI.

Keywords

Cardiovascular disease Genetic variation Myocardial infarction Mortality Haplotype Inflammation 

Abbreviations list

AMI

Acute myocardial infarction

BMDM

Bone marrow-derived macrophages

CAD

Coronary artery disease

GWAS

Genome-wide association study

HWE

Hardy–Weinberg equilibrium

PVD

Peripheral vascular disease

LD

Linkage disequilibrium

MACE

Major adverse cardiac events

Notes

Funding

This work and Dr. Cresci’s effort are supported in part by the National Institutes of Health (Cresci R01 NR013396). TRIUMPH was sponsored by the National Institutes of Health: Washington University School of Medicine SCCOR Grant P50 HL077113. Dr. Coverstone’s effort is supported in part by the National Institutes of Health: National Research Service Award 5-T32-HL07081-38 from the National Heart, Lung, and Blood Institute (NHLBI) and Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health. Dr. Bierut’s effort is supported in part by the National Institutes of Health (R01 DA025888 and R01 DA036583). The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. Dr. Sucharov's effort is supported in part by the National Institutes of Health R01 HL107715 and American Heart Association  13GRNT16950045.

Compliance with ethical standards

Conflict of interest

Edward Coverstone: None. Richard G. Bach: Research Grants: Novartis, MyoKardia. Consultant (Clinical Event Committee activity only): Novo Nordisk, Pharmacosmos NA. LiShiun Chen: None. Laura J. Bierut: Copyrights/Patents: Listed as an inventor on Issued U.S. Patent 8080,371,“Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. Allie Y. Li: None. Petra A. Lenzini: None. Heidi C. O'Neill: None. John A. Spertus: Research Grants: Eli Lilly, EveHeart, Genentech, Gilead. Consultant: St. Jude Medical, United Healthcare, Amgen, Genentech, Janssen. Copyrights/Patents: Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, Peripheral Artery Questionnaire, US Patents: 7643,969; 7,853,456; 12/965,656; 13/615,401. Carmen Sucharov: Scientific founder and shareholder, CoramiR Inc. and miRagen Inc. Jerry Stitzel: Research grants: Pfizer. Joel Schilling: None. Sharon Cresci: None.

Supplementary material

395_2018_697_MOESM1_ESM.docx (239 kb)
Supplementary material 1 (DOCX 239 kb)

References

  1. 1.
    Andreassi MG, Adlerstein D, Carpeggiani C, Shehi E, Fantinato S, Ghezzi E, Botto N, Coceani M, L’Abbate A (2012) Individual and summed effects of high-risk genetic polymorphisms on recurrent cardiovascular events following ischemic heart disease. Atherosclerosis 223:409–415.  https://doi.org/10.1016/j.atherosclerosis.2012.05.029 CrossRefPubMedGoogle Scholar
  2. 2.
    Arnold SV, Chan PS, Jones PG, Decker C, Buchanan DM, Krumholz HM, Ho PM, Spertus JA, Consortium COR (2011) Translational research investigating underlying disparities in acute myocardial infarction patients’ health status (TRIUMPH) design and rationale of a prospective multicenter registry. Circ-Cardiovasc Qual 4:467–476.  https://doi.org/10.1161/Circoutcomes.110.960468 CrossRefGoogle Scholar
  3. 3.
    Bagdas D, AlSharari SD, Freitas K, Tracy M, Damaj MI (2015) The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain. Biochem Pharmacol 97:590–600.  https://doi.org/10.1016/j.bcp.2015.04.013 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Bierut LJ, Stitzel JA, Wang JC, Hinrichs AL, Grucza RA, Xuei XL, Saccone NL, Saccone SF, Bertelsen S, Fox L, Horton WJ, Breslau N, Budde J, Cloninger CR, Dick DM, Foroud T, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Kuperman S, Madden PAF, Mayo K, Nurnberger J, Pomerleau O, Porjesz B, Reyes O, Schuckit M, Swan G, Tischfield JA, Edenberg HJ, Rice JP, Goate AM (2008) Variants in nicotinic receptors and risk for nicotine dependence. Am J Psychiatry 165:1163–1171.  https://doi.org/10.1176/appi.ajp.2008.07111711 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans D, Leung HT, Marchini JL, Morris AP, Spencer CCA, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O’Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP et al (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678.  https://doi.org/10.1038/nature05911 CrossRefGoogle Scholar
  6. 6.
    Calvillo L, Vanoli E, Andreoli E, Besana A, Omodeo E, Gnecchi M, Zerbi P, Vago G, Busca G, Schwartz PJ (2011) Vagal stimulation, through its nicotinic action, limits infarct size and the inflammatory response to myocardial ischemia and reperfusion. J Cardiovasc Pharmacol 58:500–507.  https://doi.org/10.1097/FJC.0b013e31822b7204 CrossRefPubMedGoogle Scholar
  7. 7.
    Chen LS, Bach RG, Lenzini PA, Spertus JA, Bierut LJ, Cresci S (2014) CHRNA5 variant predicts smoking cessation in patients with acute myocardial infarction. Nicotine Tob Res 16:1224–1231.  https://doi.org/10.1093/ntr/ntu059 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Chen LS, Baker TB, Piper ME, Breslau N, Cannon DS, Doheny KF, Gogarten SM, Johnson E, Saccone NL, Wang JC, Weiss RB, Goate AM, Bierut LJ (2012) Interplay of genetic risk factors (CHRNA5-CHRNA3-CHRNB4) and Cessation treatments in smoking cessation success. Am J Psychiatry 169:735–742.  https://doi.org/10.1176/appi.ajp.2012.11101545 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cresci S, Dorn GW, Jones PG, Beitelshees AL, Li AY, Lenzini PA, Province MA, Spertus JA, Lanfear DE (2012) Adrenergic-pathway gene variants influence beta-blocker-related outcomes after acute coronary syndrome in a race-specific manner. J Am Coll Cardiol 60:898–907.  https://doi.org/10.1016/j.jacc.2012.02.051 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cresci S, Wu J, Province MA, Spertus JA, Steffes M, McGill JB, Alderman EL, Brooks MM, Kelsey SF, Frye RL, Bach RG, Grp BDS (2011) Peroxisome proliferator-activated receptor pathway gene polymorphism associated with extent of coronary artery disease in patients with type 2 diabetes in the bypass angioplasty revascularization investigation 2 diabetes trial. Circulation 124:1426-U1173.  https://doi.org/10.1161/Circulationaha.111.029173 CrossRefGoogle Scholar
  11. 11.
    De Nardo D, Latz E (2011) NLRP3 inflammasomes link inflammation and metabolic disease. Trends Immunol 32:373–379.  https://doi.org/10.1016/j.it.2011.05.004 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Depta JP, Lenzini PA, Lanfear DE, Wang TY, Spertus JA, Bach RG, Cresci S (2015) Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction. Pharmacogenom J 15:20–25.  https://doi.org/10.1038/tpj.2014.28 CrossRefGoogle Scholar
  13. 13.
    Ellis KL, Pilbrow AP, Frampton CM, Doughty RN, Whalley GA, Ellis CJ, Palmer BR, Skelton L, Yandle TG, Palmer SC, Troughton RW, Richards AM, Cameron VA (2010) A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality. CircCardiovascGenet 3:286–293.  https://doi.org/10.1161/CIRCGENETICS.109.917443 CrossRefGoogle Scholar
  14. 14.
    Frankel DS, Meigs JB, Massaro JM, Wilson PWF, O’Donnell CJ, D’Agostino RB, Tofler GH (2008) Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease the framingham offspring study. Circulation 118:2533–2539.  https://doi.org/10.1161/Circulationaha.108.792986 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Heron M (2013) Deaths: leading causes for 2010. NatlVital StatRep 62:1–97Google Scholar
  16. 16.
    Heusch G, Gersh BJ (2017) The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J 38:774–784.  https://doi.org/10.1093/eurheartj/ehw224 PubMedCrossRefGoogle Scholar
  17. 17.
    Hoppmann P, Erl A, Turk S, Tiroch K, Mehilli J, Schomig A, Kastrati A, Koch W (2009) No association of chromosome 9p21.3 variation with clinical and angiographic outcomes after placement of drug-eluting stents. Jacc-Cardiovasc Interv 2:1149–1155.  https://doi.org/10.1016/j.jcin.2009.08.021 CrossRefPubMedGoogle Scholar
  18. 18.
    Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, Izawa A, Takahashi Y, Masumoto J, Koyama J, Hongo M, Noda T, Nakayama J, Sagara J, Taniguchi S, Ikeda U (2011) Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123:594–604.  https://doi.org/10.1161/CIRCULATIONAHA.110.982777 CrossRefPubMedGoogle Scholar
  19. 19.
    Lanfear DE, Jones PG, Cresci S, Tang FM, Rathore SS, Spertus JA (2011) Factors influencing patient willingness to participate in genetic research after a myocardial infarction. Genome Med 3:39.  https://doi.org/10.1186/gm255 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Li WL, Hua LG, Qu P, Yan WH, Ming C, Jun YD, Yuan LD, Nan N (2016) NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis. Arch Med Sci 12:950–958.  https://doi.org/10.5114/aoms.2016.61356 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408.  https://doi.org/10.1006/meth.2001.1262 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Marchetti C, Chojnacki J, Toldo S, Mezzaroma E, Tranchida N, Rose SW, Federici M, Van Tassell BW, Zhang S, Abbate A (2014) A novel pharmacologic inhibitor of the NLRP3 inflammasome limits myocardial injury after ischemia-reperfusion in the mouse. J Cardiovasc Pharmacol 63:316–322.  https://doi.org/10.1097/FJC.0000000000000053 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    McNamara RL, Kennedy KF, Cohen DJ, Diercks DB, Moscucci M, Ramee S, Wang TY, Connolly T, Spertus JA (2016) Predicting in-hospital mortality in patients with acute myocardial infarction. J Am Coll Cardiol 68:626–635.  https://doi.org/10.1016/j.jacc.2016.05.049 CrossRefPubMedGoogle Scholar
  24. 24.
    Mezzaroma E, Toldo S, Farkas D, Seropian IM, Van Tassell BW, Salloum FN, Kannan HR, Menna AC, Voelkel NF, Abbate A (2011) The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci USA 108:19725–19730.  https://doi.org/10.1073/pnas.1108586108 CrossRefPubMedGoogle Scholar
  25. 25.
    Morgan TM, House JA, Cresci S, Jones P, Allayee H, Hazen SL, Patel Y, Patel RS, Eapen DJ, Waddy SP, Quyyumi AA, Kleber ME, Marz W, Winkelmann BR, Boehm BO, Krumholz HM, Spertus JA (2011) Investigation of 95 variants identified in a genome-wide study for association with mortality after acute coronary syndrome. BMC Med Genet 12:127.  https://doi.org/10.1186/1471-2350-12-127 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Moss AJ, Ryan D, Oakes D, Goldstein RE, Greenberg H, Bodenheimer MM, Brown MW, Case RB, Dwyer EM, Eberly SW, Francis CW, Gillespie JA, Krone RJ, Lichstein E, MacCluer JW, Marcus FI, McCarthy J, Sparks CW, Zareba W (2005) Atherosclerotic risk genotypes and recurrent coronary events after myocardial infarction. Am J Cardiol 96:177–182.  https://doi.org/10.1016/j.amjcard.2005.03.039 CrossRefPubMedGoogle Scholar
  27. 27.
    Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047.  https://doi.org/10.1084/jem.20070885 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Pickard JM, Burke N, Davidson SM, Yellon DM (2017) Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning. Basic Res Cardiol 112:11.  https://doi.org/10.1007/s00395-017-0601-x CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Pickard JM, Davidson SM, Hausenloy DJ, Yellon DM (2016) Co-dependence of the neural and humoral pathways in the mechanism of remote ischemic conditioning. Basic Res Cardiol 111:50.  https://doi.org/10.1007/s00395-016-0568-z CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Saccone NL, Culverhouse RC, Schwantes-An TH, Cannon DS, Chen XN, Cichon S, Giegling I, Han SZ, Han YH, Keskitalo-Vuokko K, Kong XY, Landi MT, Ma JZ, Short SE, Stephens SH, Stevens VL, Sun LW, Wang YF, Wenzlaff AS, Aggen SH, Breslau N, Broderick P, Chatterjee N, Chen JC, Heath AC, Heliovaara M, Hoft NR, Hunter DJ, Jensen MK, Martin NG, Montgomery GW, Niu TH, Payne TJ, Peltonen L, Pergadia ML, Rice JP, Sherva R, Spitz MR, Sun JZ, Wang JC, Weiss RB, Wheeler W, Witt SH, Yang BZ, Caporaso NE, Ehringer MA, Eisen T, Gapstur SM, Gelernter J, Houlston R, Kaprio J, Kendler KS, Kraft P, Leppert MF, Li MD, Madden PAF, Nothen MM, Pillai S, Rietschel M, Rujescu D, Schwartz A, Amos CI, Bierut LJ (2010) Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD. PLoS Genet.  https://doi.org/10.1371/journal.pgen.1001053 PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Scheet P, Stephens M (2006) A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase. Am J Hum Genet 78:629–644.  https://doi.org/10.1086/502802 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Selvin S (1991) Statistical analysis of epidemiologic data. Oxford University Press, New YorkGoogle Scholar
  33. 33.
    Takeshita S, Kaji K, Kudo A (2000) Identification and characterization of the new osteoclast progenitor with macrophage phenotypes being able to differentiate into mature osteoclasts. J Bone Miner Res 15:1477–1488.  https://doi.org/10.1359/jbmr.2000.15.8.1477 CrossRefPubMedGoogle Scholar
  34. 34.
    Thorgeirsson TE, Geller F, Sulem P, Rafnar T, Wiste A, Magnusson KP, Manolescu A, Thorleifsson G, Stefansson H, Ingason A, Stacey SN, Bergthorsson JT, Thorlacius S, Gudmundsson J, Jonsson T, Jakobsdottir M, Saemundsdottir J, Olafsdottir O, Gudmundsson LJ, Bjornsdottir G, Kristjansson K, Skuladottir H, Isaksson HJ, Gudbjartsson T, Jones GT, Mueller T, Gottsater A, Flex A, Aben KKH, de Vegt F, Mulders PFA, Isla D, Vidal MJ, Asin L, Saez B, Murillo L, Blondal T, Kolbeinsson H, Stefansson JG, Hansdottir I, Runarsdottir V, Pola R, Lindblad B, van Rij AM, Dieplinger B, Haltmayer M, Mayordomo JI, Kiemeney LA, Matthiasson SE, Oskarsson H, Tyrfingsson T, Gudbjartsson DF, Gulcher JR, Jonsson S, Thorsteinsdottir U, Kong A, Stefansson K (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452:638-U639.  https://doi.org/10.1038/nature06846 CrossRefGoogle Scholar
  35. 35.
    Toldo S, Mezzaroma E, Mauro AG, Salloum F, Van Tassell BW, Abbate A (2015) The inflammasome in myocardial injury and cardiac remodeling. Antioxid Redox Signal 22:1146–1161.  https://doi.org/10.1089/ars.2014.5989 CrossRefPubMedGoogle Scholar
  36. 36.
    Topol EJ (2005) Simon Dack Lecture. The genomic basis of myocardial infarction. J Am Coll Cardiol 46:1456–1465.  https://doi.org/10.1016/j.jacc.2005.06.064 CrossRefPubMedGoogle Scholar
  37. 37.
    Tregouet DA, Tiret L (2004) Cox proportional hazards survival regression in haplotype-based association analysis using the stochastic-EM algorithm. Eur J Hum Genet 12:971–974.  https://doi.org/10.1038/sj.ejhg.5201238 CrossRefPubMedGoogle Scholar
  38. 38.
    Uhlen M, Bjorling E, Agaton C, Szigyarto CA, Amini B, Andersen E, Andersson AC, Angelidou P, Asplund A, Asplund C, Berglund L, Bergstrom K, Brumer H, Cerjan D, Ekstrom M, Elobeid A, Eriksson C, Fagerberg L, Falk R, Fall J, Forsberg M, Bjorklund MG, Gumbel K, Halimi A, Hallin I, Hamsten C, Hansson M, Hedhammar M, Hercules G, Kampf C, Larsson K, Lindskog M, Lodewyckx W, Lund J, Lundeberg J, Magnusson K, Malm E, Nilsson P, Odling J, Oksvold P, Olsson I, Oster E, Ottosson J, Paavilainen L, Persson A, Rimini R, Rockberg J, Runeson M, Sivertsson A, Skollermo A, Steen J, Stenvall M, Sterky F, Stromberg S, Sundberg M, Tegel H, Tourle S, Wahlund E, Walden A, Wan J, Wernerus H, Westberg J, Wester K, Wrethagen U, Xu LL, Hober S, Ponten F (2005) A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteom 4:1920–1932.  https://doi.org/10.1074/mcp.M500279-MCP200 CrossRefGoogle Scholar
  39. 39.
    Uitterdijk A, Yetgin T, te Lintel Hekkert M, Sneep S, Krabbendam-Peters I, van Beusekom HM, Fischer TM, Cornelussen RN, Manintveld OC, Merkus D, Duncker DJ (2015) Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow. Basic Res Cardiol 110:508.  https://doi.org/10.1007/s00395-015-0508-3 CrossRefPubMedGoogle Scholar
  40. 40.
    Vida G, Pena G, Deitch EA, Ulloa L (2011) Alpha7-cholinergic receptor mediates vagal induction of splenic norepinephrine. J Immunol 186:4340–4346.  https://doi.org/10.4049/jimmunol.1003722 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Virani SS, Brautbar A, Lee VV, MacArthur E, Morrison AC, Grove ML, Nambi V, Frazier L, Wilson JM, Willerson JT, Boerwinkle E, Ballantyne CM (2012) Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circ J 76:950–956.  https://doi.org/10.1253/circj.CJ-11-1166 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388.  https://doi.org/10.1038/nature01339 CrossRefPubMedGoogle Scholar
  43. 43.
    Wang JC, Cruchaga C, Saccone NL, Bertelsen S, Liu PY, Budde JP, Duan WM, Fox L, Grucza RA, Kern J, Mayo K, Reyes O, Rice J, Saccone SF, Spiegel N, Steinbach JH, Stitzel JA, Anderson MW, You M, Stevens VL, Bierut LJ, Goate AM, Collaborators C, Collaborators G (2009) Risk for nicotine dependence and lung cancer is conferred by mRNA expression levels and amino acid change in CHRNA5. Hum Mol Genet 18:3125–3135.  https://doi.org/10.1093/hmg/ddp231 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Wang L, Zheng J, Bai X, Liu B, Liu CJ, Xu QB, Zhu Y, Wang NP, Kong W, Wang X (2009) ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries. Circ Res 104:688-U247.  https://doi.org/10.1161/Circresaha.108.188425 CrossRefGoogle Scholar
  45. 45.
    Wauters E, Carruthers KF, Buysschaert I, Dunbar DR, Peuteman G, Belmans A, Budaj A, Van de Werf F, Lambrechts D, Fox KAA (2013) Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study. Eur Heart J 34:993–1001.  https://doi.org/10.1093/eurheartj/ehs389 CrossRefPubMedGoogle Scholar
  46. 46.
    Weber K, Schilling JD (2014) Distinct lysosome phenotypes influence inflammatory function in peritoneal and bone marrow-derived macrophages. Int J Inflam 2014:154936.  https://doi.org/10.1155/2014/154936 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yan AT, Yan RT, Tan M, Eagle KA, Granger CB, Dabbous OH, Fitchett D, Grima E, Langer A, Goodman SG, Acs, (2005) In-hospital revascularization and one-year outcome of acute coronary syndrome patients stratified by the GRACE risk score. Am J Cardiol 96:913–916.  https://doi.org/10.1016/j.amjcard.2005.05.046 CrossRefPubMedGoogle Scholar
  48. 48.
    Yang J, Zhu Y, Cole SA, Haack K, Zhang Y, Beebe LA, Howard BV, Best LG, Devereux RB, Henderson JA, Henderson P, Lee ET, Zhao J (2012) A gene-family analysis of 61 genetic variants in the nicotinic acetylcholine receptor genes for insulin resistance and type 2 diabetes in American Indians. Diabetes 61:1888–1894.  https://doi.org/10.2337/db11-1393 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Yang JY, Zhu Y, Lee ET, Zhang Y, Cole SA, Haack K, Best LG, Devereux RB, Roman MJ, Howard BV, Zhao JY (2013) Joint associations of 61 genetic variants in the nicotinic acetylcholine receptor genes with subclinical atherosclerosis in American Indians a gene-family analysis. Circ-Cardiovasc Gene 6:89–96.  https://doi.org/10.1161/Circgenetics.112.963967 CrossRefGoogle Scholar
  50. 50.
    Zhang J, Summah H, Zhu YG, Qu JM (2011) Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis. Respir Res 12:158.  https://doi.org/10.1186/1465-9921-12-158 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Zhao M, He X, Bi XY, Yu XJ, Gil Wier W, Zang WJ (2013) Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res Cardiol 108:345.  https://doi.org/10.1007/s00395-013-0345-1 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Edward D. Coverstone
    • 1
  • Richard G. Bach
    • 1
  • LiShiun Chen
    • 3
  • Laura J. Bierut
    • 3
  • Allie Y. Li
    • 1
  • Petra A. Lenzini
    • 4
  • Heidi C. O’Neill
    • 7
  • John A. Spertus
    • 5
  • Carmen C. Sucharov
    • 6
  • Jerry A. Stitzel
    • 7
  • Joel D. Schilling
    • 1
    • 8
  • Sharon Cresci
    • 1
    • 2
  1. 1.Cardiovascular Division, Department of MedicineWashington University School of MedicineSaint LouisUSA
  2. 2.Department of GeneticsWashington University School of MedicineSaint LouisUSA
  3. 3.Department of PsychiatryWashington University School of MedicineSaint LouisUSA
  4. 4.Statistical Genomics Division, Department of GeneticsWashington University School of MedicineSaint LouisUSA
  5. 5.Saint Luke’s Mid America Heart Institute and the University of Missouri-Kansas CityKansas CityUSA
  6. 6.Cardiology Division, Department of MedicineUniversity of Colorado DenverAuroraUSA
  7. 7.Institute for Behavioral Genetics, University of ColoradoBoulderUSA
  8. 8.Department of Pathology and ImmunologyWashington University School of MedicineSaint LouisUSA

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