Cardiomyocyte microvesicles: proinflammatory mediators after myocardial ischemia?
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Cardiomyocyte microvesicles: proinflammatory mediators after myocardial ischemia? Patrick Malcolm Siegel1,2 · Judith Schmich1,2 · Georg Barinov1 · István Bojti1 · Christopher Vedecnik1 · Novita Riani Simanjuntak1 · Christoph Bode1 · Martin Moser1 · Karlheinz Peter2,3 · Philipp Diehl1,2,3
© Springer Science+Business Media, LLC, part of Springer Nature 2020
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. H9c2cells 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. Keywords C-reactive protein · Myocardial infarction · Microvesicles · Cardiomyocytes
Highlights
• Cardiomyocyte microvesicles contain a distinct set of
• Microvesicle release from cardiomyocytes is increased
• CMV contain inflammation associated miRNA • CMV stimulate IL-6 expression in THP-1 macrophages • CMV stimulate CRP expression in a hepatic co-culture
during hypoxia
Karlheinz Peter and Philipp Diehl have contributed equally. * Patrick Malcolm Siegel patrick.siegel@universitaets‑herzzentrum.de 1
Cardiology and Angiology I, Heart Center Freiburg University, Medical Faculty, University of Freiburg, 79106 Freiburg im Breisgau, Germany
2
Baker Heart & Diabetes Institute, Atherothrombosis & Vascular Biology Laboratory, Melbourne, Australia
3
Faculty for Medicine & Nursing, Monash University, Melbourne, Australia
miRNA from their parent cells
model
Introduction Cardiovascular disease and myocardial infarction in particular, are the leading cause of mortality worldw
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