Abstract 416: G Protein-coupled Receptor 15 is Associated with Inflammation, Smoking and Ischemia
Introduction: The mechanisms leading to myocardial infarction (MI) are still not fully understood. As the orphan G protein-coupled receptor 15 (GPR15) gene has recently been shown to be hypomethylated in smokers as well as to be involved in inflammation, it poses a new candidate gene for cardiovascular disease.
Hypothesis: We hypothesized that GPR15 influences the development of MI via smoking and inflammation.
Methods: To investigate the effect of smoking and changes in expression over time, monocytic GPR15 mRNA expression was measured in smokers (n = 273), ex-smokers (n = 533) and never-smokers (n = 687) from the Gutenberg Health Study (GHS) via qPCR.
In order to assess GPR15 expression after MI, mRNA expression in peripheral blood mononuclear cells was compared between 112 young MI cases (< 50 years) and 112 controls from the GHS using the Affymetrix Exon ST1.0 GeneChip Array. Subsequently, cardiac GPR15 expression in mouse models of MI (n = 8), myocarditis (n = 8), hypertrophy (n = 6) and untreated controls was measured via qPCR.
Results: GPR15 expression was significantly increased in smokers compared to never-smokers (16.0 ± 2.4-fold, p < 0.001). Ex-smokers still had significantly elevated GPR15 expression levels compared to never-smokers up to ten years after quitting (3.9 ± 0.9-fold, p < 0.001).
Furthermore, GPR15 expression was 1.43-fold higher in young MI patients compared to controls (± 0.09-fold, p = 1.9*10-7). Likewise, mouse Gpr15 expression was significantly elevated in infarcted hearts (6.3 ± 1.1 fold, p < 0.05) and in inflamed hearts (10.2 ± 2.5 fold, p < 0.01) but not in the hypertrophic hearts (1.0 ± 0.3) compared to controls.
Conclusion: Consistent with literature on GPR15 methylation, GPR15 expression was increased in smokers, but also after inflammation and ischemia, independently of smoking. In conclusion, GPR15 might play a role in the development of myocardial infarction via smoking and inflammatory mechanisms.
Author Disclosures: T. Haase: None. C. Müller: None. A. Schillert: None. D. Lindner: None. R. Schnabel: None. P. Wild: None. K. Lackner: None. T. Münzel: None. D. Westermann: None. A. Ziegler: None. S. Blankenberg: None. T. Zeller: None.
- © 2015 by American Heart Association, Inc.