IMR Press / FBL / Volume 21 / Issue 1 / DOI: 10.2741/4383

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Caspase-1 mediates hyperlipidemia-weakened progenitor cell vessel repair

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1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, China
2 Department of Cardiology, The Second affiliated hospital to Nanchang University, Nanchang, JiangXi 330006, China
3 Center for Metabolic Disease Research, Department of Pharmacology, Thrombosis Research Center, Philadelphia, PA 19140, USA
4 Cardiovascular Research Center, Philadelphia, PA 19140, USA
5 Center for Translational Medicine, Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA
Academic Editor:Xiao-Feng Yang
Front. Biosci. (Landmark Ed) 2016, 21(1), 178–191; https://doi.org/10.2741/4383
Published: 1 January 2016
Abstract

Caspase-1 activation senses metabolic danger-associated 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 hyperlipidemia-induced 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.

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