Circulation Research. 2003;93:907-916
doi: 10.1161/01.RES.0000100390.68771.CC
doi: 10.1161/01.RES.0000100390.68771.CC
© 2003 American Heart Association, Inc.
Reviews |
Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System
Insights From Genetically Modified Mice
From the Institut für Pharmakologie und Toxikologie (R.F., F.H.), Technische Universität, München, Germany; Institute of Clinical Biochemistry and Pathobiochemistry (S.M.L., U.W.), University of Würzburg, Germany; and Department of Biochemistry (H.d.J.), Erasmus University Medical Center, Rotterdam, The Netherlands.
Correspondence to Franz Hofmann, Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Str. 29, D-80802 München, Germany. E-mail Hofmann{at}ipt.med.tu-muenchen.de
Rudi F. Busse Editor
This Review is part of a thematic series on Cyclic GMP-Generating Enzymes and Cyclic GMP-Dependent Signaling, which includes the following articles:
Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase
Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function
Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A
Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System: Insights From Genetically Modified Mice
Regulation of Gene Expression by Cyclic GMP
Explaining the Phenomenon of Nitrate Tolerance
Signaling cascades initiated by nitric oxide (NO) and natriuretic peptides (NPs) play an important role in the maintenance of cardiovascular homeostasis. It is currently accepted that many effects of these endogenous signaling molecules are mediated via stimulation of guanylyl cyclases and intracellular production of the second messenger cGMP. Indeed, cGMP-elevating drugs like glyceryl trinitrate have been used for more than 100 years to treat cardiovascular diseases. However, the molecular mechanisms of NO/NP signaling downstream of cGMP are not completely understood. Recent in vitro and in vivo evidence identifies cGMP-dependent protein kinases (cGKs) as major mediators of cGMP signaling in the cardiovascular system. In particular, the analysis of conventional and conditional knockout mice indicates that cGKs are critically involved in regulating vascular remodeling and thrombosis. Thus, cGKs may represent novel drug targets for the treatment of human cardiovascular disorders.
Key Words: smooth muscle relaxation • cGMP • nitric oxide • atherosclerosis • cardiac hypertrophy
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