Caspase-1 mediates hyperlipidemia-weakened progenitor cell vessel repair

Ya Feng Li, Xiao Huang, Xinyuan Li, Ren Gong, Ying Yin, Jun Nelson, Erhe Gao, Hongyu Zhang, Nicholas E. Hoffman, Steven R. Houser, Muniswamy Madesh, Douglas G. Tilley, Eric T. Choi, Xiaohua Jiang, Cong Xin Huang, Hong Wang, Xiao Feng Yang

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Caspase-1 activation senses metabolic dangerassociated molecular patterns (DAMPs) and mediates the initiation of inflammation in endothelial cells. Here, we examined whether the caspase-1 pathway is responsible for sensing hyperlipidemia as a DAMP in bone marrow (BM)-derived Stem cell antigen-1 positive (Sca-1+) stem/progenitor cells and weakening their angiogenic ability. Using biochemical methods, gene knockout, cell therapy and myocardial infarction (MI) models, we had the following findings: 1) Hyperlipidemia induces caspase-1 activity in mouse Sca-1+ progenitor cells in vivo; 2) Caspase-1 contributes to hyperlipidemiainduced modulation of vascular cell death-related gene expression in vivo; 3) Injection of Sca-1+ progenitor cells from caspase-1-/- mice improves endothelial capillary density in heart and decreases cardiomyocyte death in a mouse model of MI; and 4) Caspase-1-/- Sca-1+ progenitor cell therapy improves mouse cardiac function after MI. Our results provide insight on how hyperlipidemia activates caspase-1 in Sca-1+ progenitor cells, which subsequently weakens Sca-1+ progenitor cell repair of vasculature injury. These results demonstrate the therapeutic potential of caspase-1 inhibition in improving progenitor cell therapy for MI.

Original languageEnglish (US)
Pages (from-to)178-191
Number of pages14
JournalFrontiers in Bioscience - Landmark
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Angiogenesis
  • Caspase-1 activation
  • Hyperlipidemia
  • Myocardial infarction
  • Stem cell therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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