Journal article

Publication year: 2009

Pages: 381-387

Journal: Cardiovascular Research

Volume number: 83

Issue number: 2

ISSN: 0008-6363

eISSN: 1755-3245

Open access status: Bronze

DOI Link: https://doi.org/10.1093/cvr/cvp065

Publisher: Oxford University Press

Abstract: 

Ischaemia-reperfusion provokes barrier failure of the coronary microvasculature, impeding functional recovery of the heart during reperfusion. The aim of the present study was to investigate whether the stimulation of cGMP signalling by activation of soluble guanylyl cyclase (sGC) can reduce reperfusion-induced endothelial intercellular gap formation and to determine whether this is due to an influence on endothelial cytosolic Ca2+ homeostasis during reperfusion.

Experiments were performed with cultured coronary endothelial monolayers and isolated saline-perfused rat hearts. HMR1766 (1 mu mol/L) or DEAnonoate (0.5 mu mol/L) were used to activate sGC. After exposure to simulated ischaemic conditions, reperfusion of endothelial cells led to a pronounced increase in cytosolic calcium levels and intercellular gaps. Stimulation of cGMP signalling during reperfusion increased Ca2+ sequestration in the endoplasmic reticulum (ER) and attenuated the reperfusion-induced increase in cytosolic [Ca2+]. Phosphorylation of phospholamban was also increased, indicating a de-inhibition of the ER Ca2+ pump (SERCA). Reperfusion-induced intercellular gap formation was reduced. Reduction of myosin light chain phosphorylation indicated inactivation of the endothelial contractile machinery. Effects on cytsolic Ca2+ and gaps were abrogated by inhibition of cGMP-dependent protein kinase (PKG) with KT5823. In reperfused hearts, stimulation of cGMP signalling led to decreased oedema development.

sGC/PKG activation during reperfusion reduces reperfusion-induced endothelial intercellular gap formation by attenuation of cytosolic calcium overload and reduction of contractile activation in endothelial cells. This mechanism protects the heart against reperfusion-induced oedema.

Harvard Citation style: Kasseckert, S., Schaefer, C., Kluger, A., Gligorievski, D., Tillmann, J., Schlueter, K., et al. (2009) Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation, Cardiovascular Research, 83(2), pp. 381-387. https://doi.org/10.1093/cvr/cvp065

APA Citation style: Kasseckert, S., Schaefer, C., Kluger, A., Gligorievski, D., Tillmann, J., Schlueter, K., Noll, T., Sauer, H., Piper, H., & Abdallah, Y. (2009). Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation. Cardiovascular Research. 83(2), 381-387. https://doi.org/10.1093/cvr/cvp065