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Psychoneuroimmunology (PNI) is a multidisciplinary field that examines how psychological factors, particularly stress, interact with the immune system and impact physical health. Research in PNI has shown that chronic or traumatic stress can disrupt both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. These disruptions contribute to serious health conditions, including cardiovascular diseases.
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PD-1/PD-L1 and coronary heart disease: a mendelian randomization study.

Liangjia Zeng1,2,3, Yinglan Liang3,4, Ruoyun Zhou2,3

  • 1The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

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Programmed cell death protein-1 (PD-1) and its ligand PD-L1 show a causal link with chronic ischemic heart disease. This study reveals a bidirectional relationship between PD-1 and chronic ischemic heart disease, and a protective effect of PD-L1.

Keywords:
GSEAMendelian randomization (MR)PD-1PD-L1coronary heart disease (CHD)

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Area of Science:

  • Immunology
  • Cardiovascular Medicine
  • Genetics

Background:

  • Programmed cell death protein-1 (PD-1) and its ligand PD-L1 are implicated in coronary heart disease (CHD) pathogenesis.
  • Understanding the causal relationship between PD-1/PD-L1 and specific CHDs is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the causal relationship between PD-1/PD-L1 and five specific types of coronary heart disease using Mendelian randomization.
  • To validate findings through gene set enrichment analysis (GSEA).

Main Methods:

  • Mendelian randomization (MR) analysis utilizing summary-level data from UK Biobank and large genome-wide association studies (GWAS).
  • Employed inverse variance-weighted (IVW) meta-analysis, weighted median, MR-Egger, and MR-PRESSO methods.
  • Conducted sensitivity analyses including MR-Egger intercept, Cochran's Q test, and leave-one-out analysis.
  • Performed GSEA using gene expression data from the GEO database (GSE71226).

Main Results:

  • A significant bidirectional causal association was found between PD-1 and chronic ischemic heart disease (CIHD).
  • A significant protective association was identified between PD-L1 and CIHD.
  • No significant causal relationships were observed between PD-1/PD-L1 and acute myocardial infarction, angina pectoris, coronary atherosclerosis, or unstable angina pectoris.
  • GSEA indicated downregulation of the 'PD-L1 expression and PD-1 checkpoint pathway in cancer' in CHD.

Conclusions:

  • This study provides genetic evidence for a bidirectional causal link between PD-1 and chronic ischemic heart disease.
  • A protective association exists between chronic ischemic heart disease and PD-L1.
  • The findings suggest that the PD-1/PD-L1 pathway may be a relevant target for managing chronic ischemic heart disease.