Aims:

Cardiosphere-derived cells (CDCs) were cultured from human, murine and rat hearts. Their diluted supernatant improved the contractile behaviour of isolated rat cardiomyocytes (CMCs). This effect is mediated by the paracrine release of cytokines. The present study tested the hypothesis, that the cardiovascular state of the donor`s heart, in particular hypertension, influences this effect on CMCs and tries to identify the factors responsible.

Methods and Results:

CDCs were cultured from tissue samples of cardiac surgery, murine and rat hearts. The supernatant of CDCs from hypertensive humans and rats showed a higher improvement of contractile behaviour of CMCs. Subsequently, the cytokine profile of the supernatant was analysed. Among the cytokines elevated in CDCs originating from hypertensive humans or rats was Interleukin-6. CDCs were also generated from Interleukin-6^-/--mice and their wildtype littermates. The Interleukin-6^-/--CDCs-supernatant had no effect on the contractile behaviour, whereas the Interleukin-6^+/+-CDCs supernatant showed a positive effect. To confirm the hypothesis that Interleukin-6 contributes to the CDCs’ paracrine effects, CMCs were incubated with Interleukin-6. It improved the contractile function at higher concentrations. Finally, the effect of the supernatant of a hypertensive donor could be abolished by simultaneous incubation with a specific Interleukin-6 antibody.

Conclusions:

CDCs release cytokines that improve the contractile behaviour of CMCs. This effect is more distinct in CDCs from hypertensive donors and Interleukin-6 is involved in the phenomenon.