cGMP kinases and atherosclerosis

R Feil^† , W Wolfsgruber, S Feil, S Brummer, O Kuppinger and F Hofmann

Institut für Pharmakologie und Toxikologie, Technische Universität, 80802 München, Germany

author email† Presenting author

1st International Conference on cGMP. NO/sGC Interaction and its Therapeutic Implications
Leipzig, Germany, 14-16 June 2003

cGMP 2003, 1:op009

Received:	9 June 2003
Published:	3 July 2003

Oral presentation

Nitric oxide (NO) exerts both pro- and anti-atherogenic effects, but the signaling components which contribute to modulation of atherosclerosis by NO have not been identified. The cGMP-dependent protein kinase I (cGKI) is a potential mediator of vascular NO signaling. Previous in vitro studies suggested that activation of cGKI in vascular smooth muscle cells (SMCs) has an anti-atherogenic effect. Surprisingly, temporally-controlled SMC-specific disruption of the cGKI gene in mice resulted in an attenuation of atherosclerotic lesion development indicating that cGKI in SMCs promotes atherogenesis. Activation of cGKI stimulated the phenotypic modulation (proliferation and dedifferentiation) of primary aortic SMCs, probably via an interaction with the PI3K/Akt pathway. These results suggest a role of smooth muscle cGKI in the pro-atherogenic effect of NO. Inhibition of cGKI might be a therapeutic option to treat atherosclerosis in humans.

cGMP kinases and atherosclerosis

Oral presentation

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