Cardiomyocyte microvesicles: proinflammatory mediators after myocardial ischemia?

Abstract

Myocardial infarction is a frequent complication of cardiovascular disease leading to high morbidity and mortality worldwide. Elevated C-reactive protein (CRP) levels after myocardial infarction are associated with heart failure and poor prognosis. Cardiomyocyte microvesicles (CMV) are released during hypoxic conditions and can act as mediators of intercellular communication. MicroRNA (miRNA) are short non-coding RNA which can alter cellular mRNA-translation. Microvesicles (MV) have been shown to contain distinct patterns of miRNA from their parent cells which can affect protein expression in target cells. We hypothesized that miRNA containing CMV mediate hepatic CRP expression after cardiomyocyte hypoxia. H9c2-cells were cultured and murine cardiomyocytes were isolated from whole murine hearts. H9c2- and murine cardiomyocytes were exposed to hypoxic conditions using a hypoxia chamber. Microvesicles were isolated by differential centrifugation and analysed by flow cytometry. Next-generation-sequencing was performed to determine the miRNA-expression profile in H9c2 CMV compared to their parent cells. Microvesicles were incubated with a co-culture model of the liver consisting of THP-1 macrophages and HepG2 cells. IL-6 and CRP expression in the co-culture was assessed by qPCR and ELISA. CMV contain a distinct pattern of miRNA compared to their parent cells including many inflammation-related miRNA. CMV induced IL-6 expression in THP-1 macrophages alone and CRP expression in the hepatic co-culture model. MV from hypoxic cardiomyocytes can mediate CRP expression in a hepatic co-culture model. Further studies will have to show whether these effects are reproducible in-vivo.

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All data is available from the authors upon reasonable request.

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Funding

This work was supported by the German Research Foundation (DFG) and by the National Health and Medical Research Council (NHMRC) of Australia.

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Correspondence to Patrick Malcolm Siegel.

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Siegel, P.M., Schmich, J., Barinov, G. et al. Cardiomyocyte microvesicles: proinflammatory mediators after myocardial ischemia?. J Thromb Thrombolysis (2020). https://doi.org/10.1007/s11239-020-02156-x

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Keywords

  • C-reactive protein
  • Myocardial infarction
  • Microvesicles
  • Cardiomyocytes