The release of extracellular vesicles (EVs) is increased under cellular stress and
cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs
eventually reach the systemic circulation and whether their number in the bloodstream
reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic
mice expressing green fluorescent protein (GFP) by cardiomyocytes were studied in
lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome (SIRS). EVs
were separated both from platelet-free plasma and from the conditioned medium of isolated
cardiomyocytes of the left ventricular wall. Size distribution and concentration of
the released particles were determined by Nanoparticle Tracking Analysis. The presence
of GFP + cardiomyocyte-derived circulating EVs was monitored by flow cytometry and
cardiac function was assessed by echocardiography. In LPS-treated mice, systemic inflammation
and the consequent cardiomyopathy were verified by elevated plasma levels of TNF alpha,
GDF-15, and cardiac troponin I, and by a decrease in the ejection fraction. Furthermore,
we demonstrated elevated levels of circulating small- and medium-sized EVs in the
LPS-injected mice. Importantly, we detected GFP(+) cardiomyocyte-derived EVs in the
circulation of control mice, and the number of these circulating GFP(+) vesicles increased
significantly upon intraperitoneal LPS administration (P = 0.029). The cardiomyocyte-derived
GFP(+) EVs were also positive for intravesicular troponin I (cTnI) and muscle-associated
glycogen phosphorylase (PYGM). This is the first direct demonstration that cardiomyocyte-derived
EVs are present in the circulation and that the increased number of cardiac-derived
EVs in the blood reflects cardiac injury in LPS-induced systemic inflammation (SIRS).
