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  • Haase, TinaUniversity Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany (author)

G protein-coupled receptor 15 expression is associated with myocardial infarction

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2022-12-22
  • MDPI,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-211834
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-211834URI
  • https://doi.org/10.3390/ijms24010180DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case–control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Müller, ChristianUniversity Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany (author)
  • Stoffers, BastianUniversity Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany (author)
  • Kirn, PhilippGerman Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (author)
  • Waldenberger, MelanieResearch Unit Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Neuherberg, Germany (author)
  • Kaiser, Frank J.Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany (author)
  • Karakas, MahirGerman Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (author)
  • Kim, Sangwon V.Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, PA, Philadelphia, United States (author)
  • Voss, SvenjaUniversity Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany (author)
  • Wild, Philipp S.Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany (author)
  • Lackner, Karl J.German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany (author)
  • Andersson, Jonas,1977-Umeå universitet,Institutionen för folkhälsa och klinisk medicin(Swepub:umu)jasaon96 (author)
  • Söderberg, StefanUmeå universitet,Institutionen för folkhälsa och klinisk medicin(Swepub:umu)stso0001 (author)
  • Lindner, DianaUniversity Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany (author)
  • Zeller, TanjaGerman Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; University Center of Cardiovascular Science, University Heart Vascular Center Hamburg, Hamburg, Germany (author)
  • University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, GermanyGerman Centre for Cardiovascular Research (DZHK), Partner Site Hamburg, Kiel, Lübeck, Hamburg, Germany; Department of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (creator_code:org_t)

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  • In:International Journal of Molecular Sciences: MDPI24:11661-65961422-0067

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