Circulating monocyte gene expression profiles associated with cardiac remodeling and incident heart failure in the

Tess E Peterson1,2, Virginia S Hahn3, Jingzhong Ding4

  • 1Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA. tpeter@umn.edu.

Insights

Monocyte gene expression is linked to cardiac remodeling and heart failure risk. Specific gene PCCB and immunometabolism show potential for understanding non-ischemic heart failure.

Area of Science:

  • Cardiology
  • Immunology
  • Genetics

Background:

  • The role of monocytes in non-ischemic heart failure (HF) and cardiac remodeling is not well understood.
  • This study investigates monocyte gene expression in relation to cardiac metrics and HF incidence in a population free of ischemic heart disease.

Purpose of the Study:

  • To identify monocyte gene expression profiles associated with cardiac structure, function, and fibrosis.
  • To assess the association between monocyte gene expression and the risk of developing incident heart failure.

Main Methods:

  • Isolated circulating CD14+ monocytes from 1195 participants for microarray gene expression analysis.
  • Utilized contrast-enhanced cardiac MRI for cardiac structure and function assessment.
  • Employed multivariable regression and Cox regression for cross-sectional and longitudinal analyses, respectively.

Main Results:

  • Identified monocyte expression profiles linked to lymphocyte activation, cytokine production, phagocytosis, wound healing, oxidative stress, and cell migration.
  • Monocyte expression of PCCB correlated with left ventricular strain, left atrial size, myocardial fibrosis, and incident HF.
  • Mendelian randomization validated the association of PCCB expression with monocyte-specific cis-eQTLs.

Conclusions:

  • Monocyte gene expression, reflecting inflammatory and resolving activities, is associated with subclinical cardiac remodeling and fibrosis.
  • Monocyte expression of PCCB and its immunometabolism are promising targets for future research in non-ischemic heart failure.
Abstract

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