Home LiteratureArticle Details
PMID: 28750703 Published · ppublish English Journal Article Review

Translational Perspective on Epigenetics in Cardiovascular Disease.

Journal of the American College of Cardiology ·Vol. 70 ·No. 5 ·2017-08-01 ·Pages 590-606

van der Harst P, de Windt LJ, Chambers JC

Abstract

A plethora of environmental and behavioral factors interact, resulting in changes in gene expression and providing a basis for the development and progression of cardiovascular diseases. Heterogeneity in gene expression responses among cells and individuals involves epigenetic mechanisms. Advancing technology allowing genome-scale interrogation of epigenetic marks provides a rapidly expanding view of the complexity and diversity of the epigenome. In this review, the authors discuss the expanding landscape of epigenetic modifications and highlight their importance for future understanding of disease. The epigenome provides a mechanistic link between environmental exposures and gene expression profiles ultimately leading to disease. The authors discuss the current evidence for transgenerational epigenetic inheritance and summarize the data linking epigenetics to cardiovascular disease. Furthermore, the potential targets provided by the epigenome for the development of future diagnostics, preventive strategies, and therapy for cardiovascular disease are reviewed. Finally, the authors provide some suggestions for future directions.

Keywords
EWAS HAT HDAC RNA histones methylation
MeSH Terms
Cardiovascular Diseases/genetics Epigenesis, Genetic Epigenomics/methods Humans Translational Research, Biomedical
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
van der Harst Pim
Departments of Cardiology and Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Durrer Center for Cardiovascular Research, Netherlands Heart Institute, Utrecht, the Netherlands. Electronic address: [email protected].
de Windt Leon J
Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.
Chambers John C
Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Ealing Hospital NHS Trust, Middlesex, United Kingdom.
References (124)
124 references, click to expand
  1. Single-molecule decoding of combinatorially modified nucleosomes.
    Science. 2016 May 6;352(6286):717-21 PMID: 27151869
  2. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.
    Environ Health Perspect. 2006 Apr;114(4):567-72 PMID: 16581547
  3. Transgenerational epigenetic inheritance in mammals: how good is the evidence?
    FASEB J. 2016 Jul;30(7):2457-65 PMID: 27037350
  4. The widespread regulation of microRNA biogenesis, function and decay.
    Nat Rev Genet. 2010 Sep;11(9):597-610 PMID: 20661255
  5. Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs.
    Cell Rep. 2016 Feb 9;14 (5):1246-57 PMID: 26832418
  6. N6-methyladenine DNA modification in Drosophila.
    Cell. 2015 May 7;161(4):893-906 PMID: 25936838
  7. Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability.
    J Am Heart Assoc. 2016 Apr 22;5(4):null PMID: 27107129
  8. Epigenetics in the Vascular Endothelium: Looking From a Different Perspective in the Epigenomics Era.
    Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2297-306 PMID: 26404488
  9. Cardiac Myocyte De Novo DNA Methyltransferases 3a/3b Are Dispensable for Cardiac Function and Remodeling after Chronic Pressure Overload in Mice.
    PLoS One. 2015 Jun 22;10(6):e0131019 PMID: 26098432
  10. Integrative analysis of 111 reference human epigenomes.
    Nature. 2015 Feb 19;518(7539):317-30 PMID: 25693563
  11. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure.
    Circulation. 2011 Oct 4;124(14 ):1537-47 PMID: 21900086
  12. BLUEPRINT to decode the epigenetic signature written in blood.
    Nat Biotechnol. 2012 Mar 07;30(3):224-6 PMID: 22398613
  13. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.
    Nat Genet. 2015 Nov;47(11):1282-1293 PMID: 26390057
  14. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice.
    Science. 2009 Jun 26;324(5935):1710-3 PMID: 19460962
  15. Non-coding RNA: what is functional and what is junk?
    Front Genet. 2015 Jan 26;6:2 PMID: 25674102
  16. The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery.
    Cell. 2016 Nov 17;167(5):1145-1149 PMID: 27863232
  17. Disease variants alter transcription factor levels and methylation of their binding sites.
    Nat Genet. 2017 Jan;49(1):131-138 PMID: 27918535
  18. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications.
    Nat Biotechnol. 2016 Jul;34(7):726-37 PMID: 27347756
  19. Genetic sources of population epigenomic variation.
    Nat Rev Genet. 2016 Jun;17 (6):319-32 PMID: 27156976
  20. The programming of cardiovascular disease.
    J Dev Orig Health Dis. 2015 Oct;6(5):366-76 PMID: 26173733
  21. Pervasive roles of microRNAs in cardiovascular biology.
    Nature. 2011 Jan 20;469(7330):336-42 PMID: 21248840
  22. Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci.
    Hum Mol Genet. 2015 Aug 1;24(15):4464-79 PMID: 25935004
  23. Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling.
    Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2956-61 PMID: 20133625
  24. N6-methyldeoxyadenosine marks active transcription start sites in Chlamydomonas.
    Cell. 2015 May 7;161(4):879-892 PMID: 25936837
  25. Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial.
    PLoS One. 2013 Jun 26;8(6):e65744 PMID: 23840361
  26. Divergent reprogramming routes lead to alternative stem-cell states.
    Nature. 2014 Dec 11;516(7530):192-7 PMID: 25503232
  27. A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies.
    Genome Biol. 2015 Feb 15;16:37 PMID: 25853392
  28. Isoform-selective HDAC inhibitors: closing in on translational medicine for the heart.
    J Mol Cell Cardiol. 2011 Oct;51(4):491-6 PMID: 21108947
  29. Inhibition of histone deacetylases preserves myocardial performance and prevents cardiac remodeling through stimulation of endogenous angiomyogenesis.
    J Pharmacol Exp Ther. 2012 Apr;341(1):285-93 PMID: 22271820
  30. Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2.
    Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1556-1566 PMID: 24833798
  31. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment.
    Reproduction. 2014 Dec;148(6):R111-20 PMID: 25187623
  32. reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells.
    Nat Commun. 2016 Aug 17;7:12514 PMID: 27530917
  33. Intergenerational epigenetic inheritance in models of developmental programming of adult disease.
    Semin Cell Dev Biol. 2015 Jul;43:85-95 PMID: 26135290
  34. HDAC4 controls histone methylation in response to elevated cardiac load.
    J Clin Invest. 2013 Mar;123(3):1359-70 PMID: 23434587
  35. Deep RNA sequencing reveals dynamic regulation of myocardial noncoding RNAs in failing human heart and remodeling with mechanical circulatory support.
    Circulation. 2014 Mar 4;129(9):1009-21 PMID: 24429688
  36. Role of DNA Methylation in Modulating Transcription Factor Occupancy.
    Cell Rep. 2015 Aug 18;12(7):1184-95 PMID: 26257180
  37. The DNA methylation drift of the atherosclerotic aorta increases with lesion progression.
    BMC Med Genomics. 2015 Feb 27;8:7 PMID: 25881171
  38. De novo mutations in histone-modifying genes in congenital heart disease.
    Nature. 2013 Jun 13;498(7453):220-3 PMID: 23665959
  39. Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
    Nature. 2016 Feb 4;530(7588):113-6 PMID: 26814966
  40. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.
    Nature. 2017 Jan 5;541(7635):81-86 PMID: 28002404
  41. RBM20 Regulates Circular RNA Production From the Titin Gene.
    Circ Res. 2016 Oct 14;119(9):996-1003 PMID: 27531932
  42. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells.
    Cell. 2016 Nov 17;167(5):1398-1414.e24 PMID: 27863251
  43. Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study.
    Sci Rep. 2017 Jan 09;7:40377 PMID: 28067321
  44. The DNA methylation landscape of human early embryos.
    Nature. 2014 Jul 31;511(7511):606-10 PMID: 25079557
  45. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy.
    J Clin Invest. 2013 May;123(5):2143-54 PMID: 23619365
  46. HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity.
    J Biol Chem. 2008 Apr 11;283(15):10135-46 PMID: 18250163
  47. 52 Genetic Loci Influencing Myocardial Mass.
    J Am Coll Cardiol. 2016 Sep 27;68(13):1435-1448 PMID: 27659466
  48. Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis.
    J Cardiovasc Pharmacol Ther. 2016 Jan;21(1):127-37 PMID: 26130616
  49. An integrated encyclopedia of DNA elements in the human genome.
    Nature. 2012 Sep 6;489(7414):57-74 PMID: 22955616
  50. The mitochondrial side of epigenetics.
    Physiol Genomics. 2015 Aug;47(8):299-307 PMID: 26038395
  51. DNA methylation: old dog, new tricks?
    Nat Struct Mol Biol. 2014 Nov;21(11):949-54 PMID: 25372310
  52. Epigenetic regulation in heart failure: part II DNA and chromatin.
    Cardiol Rev. 2015 Nov-Dec;23(6):269-81 PMID: 26135900
  53. Epigenome-wide association study of fasting blood lipids in the Genetics of Lipid-lowering Drugs and Diet Network study.
    Circulation. 2014 Aug 12;130(7):565-72 PMID: 24920721
  54. Distinct epigenomic features in end-stage failing human hearts.
    Circulation. 2011 Nov 29;124(22):2411-22 PMID: 22025602
  55. Epigenetic Patterns in Blood Associated With Lipid Traits Predict Incident Coronary Heart Disease Events and Are Enriched for Results From Genome-Wide Association Studies.
    Circ Cardiovasc Genet. 2017 Jan;10 (1):null PMID: 28213390
  56. Inhibition of histone deacetylase on ventricular remodeling in infarcted rats.
    Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H968-77 PMID: 17400721
  57. Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors.
    J Biol Chem. 2003 Aug 1;278(31):28930-7 PMID: 12761226
  58. Histone deacetylase 3 is critical in endothelial survival and atherosclerosis development in response to disturbed flow.
    Circulation. 2010 Jan 5;121(1):132-42 PMID: 20026773
  59. Soybean ENOD40 encodes two peptides that bind to sucrose synthase.
    Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):1915-20 PMID: 11842184
  60. Landscape of transcription in human cells.
    Nature. 2012 Sep 6;489(7414):101-8 PMID: 22955620
  61. The protective role of curcumin in cardiovascular diseases.
    Int J Cardiol. 2009 Apr 3;133(2):145-51 PMID: 19233493
  62. A unique regulatory phase of DNA methylation in the early mammalian embryo.
    Nature. 2012 Mar 28;484(7394):339-44 PMID: 22456710
  63. cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes.
    Am J Physiol Cell Physiol. 2015 Sep 15;309(6):C425-36 PMID: 26224577
  64. Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster.
    Eur Heart J. 2015 Apr 21;36(16):993-1000 PMID: 25411193
  65. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9.
    N Engl J Med. 2017 Jan 5;376(1):41-51 PMID: 27959715
  66. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.
    J Am Coll Cardiol. 2014 Mar 11;63(9):920-7 PMID: 24161319
  67. Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress.
    J Pathol. 2015 Mar;235(4):606-18 PMID: 25421395
  68. Protective effect of curcumin against myocardium injury in ischemia reperfusion rats.
    Pharm Biol. 2017 Dec;55(1):1144-1148 PMID: 28224816
  69. The BLUEPRINT Data Analysis Portal.
    Cell Syst. 2016 Nov 23;3(5):491-495.e5 PMID: 27863955
  70. Histone H3 tail clipping regulates gene expression.
    Nat Struct Mol Biol. 2009 Jan;16(1):17-22 PMID: 19079264
  71. The International Human Epigenome Consortium Data Portal.
    Cell Syst. 2016 Nov 23;3(5):496-499.e2 PMID: 27863956
  72. Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats.
    Cardiovasc Res. 2014 Mar 1;101(3):373-82 PMID: 24272874
  73. Expression discordance of monozygotic twins at birth: effect of intrauterine environment and a possible mechanism for fetal programming.
    Epigenetics. 2011 May;6(5):579-92 PMID: 21358273
  74. Lysine acetyltransferase PCAF is a key regulator of arteriogenesis.
    Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1902-10 PMID: 23788761
  75. Robust validation of methylation levels association at CPT1A locus with lipid plasma levels.
    J Lipid Res. 2014 Jul;55(7):1189-91 PMID: 24850808
  76. Reading signals on the nucleosome with a new nomenclature for modified histones.
    Nat Struct Mol Biol. 2005 Feb;12(2):110-2 PMID: 15702071
  77. Detection of differentially methylated gene promoters in failing and nonfailing human left ventricle myocardium using computation analysis.
    Physiol Genomics. 2013 Jul 15;45(14 ):597-605 PMID: 23695888
  78. Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.
    Cell. 2016 Nov 17;167(5):1369-1384.e19 PMID: 27863249
  79. Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy.
    Cell. 2002 Aug 23;110(4):479-88 PMID: 12202037
  80. Ischemic heart disease and stroke in relation to blood DNA methylation.
    Epidemiology. 2010 Nov;21(6):819-28 PMID: 20805753
  81. DNA methylation and body-mass index: a genome-wide analysis.
    Lancet. 2014 Jun 7;383(9933):1990-8 PMID: 24630777
  82. Advances in the Genetics of Congenital Heart Disease: A Clinician's Guide.
    J Am Coll Cardiol. 2017 Feb 21;69(7):859-870 PMID: 28209227
  83. Circular RNAs are abundant, conserved, and associated with ALU repeats.
    RNA. 2013 Feb;19(2):141-57 PMID: 23249747
  84. A micropeptide encoded by a putative long noncoding RNA regulates muscle performance.
    Cell. 2015 Feb 12;160(4):595-606 PMID: 25640239
  85. DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States.
    Circ Res. 2016 Mar 4;118(5):786-97 PMID: 26838786
  86. DNA methylation of lipid-related genes affects blood lipid levels.
    Circ Cardiovasc Genet. 2015 Apr;8(2):334-42 PMID: 25583993
  87. Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy.
    Circulation. 2014 Mar 11;129(10):1139-51 PMID: 24396039
  88. Non-coding RNAs as regulators of gene expression and epigenetics.
    Cardiovasc Res. 2011 Jun 1;90(3):430-40 PMID: 21558279
  89. Structural basis for substrate binding and catalytic mechanism of a human RNA:m5C methyltransferase NSun6.
    Nucleic Acids Res. 2017 May 22;:null PMID: 28531330
  90. Cardiac autonomic dysfunction: particulate air pollution effects are modulated by epigenetic immunoregulation of Toll-like receptor 2 and dietary flavonoid intake.
    J Am Heart Assoc. 2015 Jan 27;4(1):e001423 PMID: 25628407
  91. Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study.
    Lancet Diabetes Endocrinol. 2015 Jul;3(7):526-534 PMID: 26095709
  92. Reversing DNA methylation: mechanisms, genomics, and biological functions.
    Cell. 2014 Jan 16;156(1-2):45-68 PMID: 24439369
  93. Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches.
    Physiol Rev. 2016 Oct;96(4):1297-325 PMID: 27535639
  94. Synthesis and biological evaluation of novel FK228 analogues as potential isoform selective HDAC inhibitors.
    Eur J Med Chem. 2016 Oct 4;121:592-609 PMID: 27318982
  95. Genome-wide methylation profiles in coronary artery ectasia.
    Clin Sci (Lond). 2017 Apr 1;131(7):583-594 PMID: 28143891
  96. Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications.
    Nat Struct Mol Biol. 2016 Jan;23(1):24-30 PMID: 26689968
  97. DNA Methylation on N6-Adenine in C. elegans.
    Cell. 2015 May 7;161(4):868-78 PMID: 25936839
  98. Competition between DNA methylation and transcription factors determines binding of NRF1.
    Nature. 2015 Dec 24;528(7583):575-9 PMID: 26675734
  99. High density methylation QTL analysis in human blood via next-generation sequencing of the methylated genomic DNA fraction.
    Genome Biol. 2015 Dec 23;16:291 PMID: 26699738
  100. Blood lipids influence DNA methylation in circulating cells.
    Genome Biol. 2016 Jun 27;17 (1):138 PMID: 27350042
  101. Readers, writers, and erasers: chromatin as the whiteboard of heart disease.
    Circ Res. 2015 Mar 27;116(7):1245-53 PMID: 25814685
  102. A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue.
    PLoS Genet. 2013 Jun;9(6):e1003572 PMID: 23825961
  103. The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies.
    Circ Res. 2016 Jan 8;118(1):119-131 PMID: 26837743
  104. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.
    Science. 2014 Sep 26;345(6204):1251086 PMID: 25258085
  105. Inhibition of Gata4 and Tbx5 by Nicotine-Mediated DNA Methylation in Myocardial Differentiation.
    Stem Cell Reports. 2017 Feb 14;8(2):290-304 PMID: 28111280
  106. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA.
    Nucleic Acids Res. 2012 Jun;40(11):5023-33 PMID: 22344696
  107. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs.
    Nat Cell Biol. 2012 Feb 12;14(3):249-56 PMID: 22327366
  108. Matrine activates PTEN to induce growth inhibition and apoptosis in V600EBRAF harboring melanoma cells.
    Int J Mol Sci. 2013 Jul 31;14 (8):16040-57 PMID: 23912239
  109. Systematic localization of common disease-associated variation in regulatory DNA.
    Science. 2012 Sep 7;337(6099):1190-5 PMID: 22955828
  110. Methylation at CPT1A locus is associated with lipoprotein subfraction profiles.
    J Lipid Res. 2014 Jul;55(7):1324-30 PMID: 24711635
  111. MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure.
    Eur J Heart Fail. 2015 Apr;17(4):405-15 PMID: 25739750
  112. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure.
    Circ Res. 2014 May 9;114(10):1569-75 PMID: 24663402
  113. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support.
    Circulation. 2009 Mar 10;119(9):1263-71 PMID: 19237659
  114. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy.
    J Clin Invest. 2014 May;124(5):2136-46 PMID: 24743145
  115. Tumor necrosis factor-alpha decreases sarcoplasmic reticulum Ca2+-ATPase expressions via the promoter methylation in cardiomyocytes.
    Crit Care Med. 2010 Jan;38(1):217-22 PMID: 19730253
  116. Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2.
    Cancer Res. 2008 Apr 1;68(7):2375-83 PMID: 18381445
  117. Histone deacetylase (HDAC) inhibition improves myocardial function and prevents cardiac remodeling in diabetic mice.
    Cardiovasc Diabetol. 2015 Aug 07;14 :99 PMID: 26245924
  118. Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling.
    J Am Heart Assoc. 2013 Apr 23;2(2):e000078 PMID: 23612897
  119. Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure.
    PLoS One. 2010 Jan 13;5(1):e8564 PMID: 20084101
  120. Cardiac ventricular chambers are epigenetically distinguishable.
    Cell Cycle. 2010 Feb 1;9(3):612-7 PMID: 20090419
  121. DNA methylation map of human atherosclerosis.
    Circ Cardiovasc Genet. 2014 Oct;7(5):692-700 PMID: 25091541
  122. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation.
    Nature. 2000 Nov 2;408(6808):106-11 PMID: 11081517
  123. Long noncoding RNA Chast promotes cardiac remodeling.
    Sci Transl Med. 2016 Feb 17;8(326):326ra22 PMID: 26888430
  124. The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in mice.
    J Clin Invest. 2011 Jun;121(6):2447-56 PMID: 21555854
Article Info
Journal
Journal of the American College of Cardiology
Abbr.
J Am Coll Cardiol
ISSN
1558-3597
DOI
10.1016/j.jacc.2017.05.067
Email
[email protected]
Published
2017-08-01
Pages
590-606
Language
English
Region
United States
NLM ID
8301365
PMCID
PMC5543329
Subset
IM
Grants
NHLBI NIH HHS · R01 HL104125 · United States
External Links
PubMed source DOI: 10.1016/j.jacc.2017.05.067 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2