Circulation. 2003;108:2172-2183
doi: 10.1161/01.CIR.0000094403.78467.C3
doi: 10.1161/01.CIR.0000094403.78467.C3
(Circulation. 2003;108:2172.)
© 2003 American Heart Association, Inc.
Special Review |
Physiology and Pathophysiology of Vascular Signaling Controlled by Cyclic Guanosine 3',5'-Cyclic Monophosphate–Dependent Protein Kinase
From the Division of Cardiology, University Hospital Eppendorf, Hamburg, Germany (T.M.); Institut für Pharmakologie und Toxikologie, Technische Universität, München, Germany (R.F., F.H.); the Institute of Cardiovascular Physiology, J.W. Goethe–University Clinic, Frankfurt/Main, Germany (A.M.); and the Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany (S.M.L., U.W.).
Correspondence to Prof Thomas Münzel, MD, Professor of Internal Medicine, Division of Cardiology, University Hospital Eppendorf, Martinistr 52, 20246 Hamburg, Germany. E-mail muenzel@uke.uni-hamburg.de
Key Words: nitric oxide • natriuretic peptides • endothelium • cardiovascular diseases • free radical
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Despite impressive medical advances1 that have led to diminished cardiovascular death rates in some countries over the past 20 years, cardiovascular disease remains the leading cause of death in developed countries such as the United States. This promises to worsen as a result of aging populations; the incipient obesity and type II diabetes epidemic; sedentary lifestyle; and continued abuse of tobacco, alcohol, and other substances. Cardiovascular disease is clearly multifactorial, and the approach to its prevention necessarily likewise. Candidates for prevention include cyclic guanosine 3',5'-cyclic monophosphate (cGMP)–dependent signaling networks initiated by natriuretic peptides (NPs) and nitric oxide (NO), which demonstrate characteristics deemed worthy of diagnostic and therapeutic exploitation. cGMP signaling contributes to the function and interaction of several vascular cell types, and its dysfunction could be involved in major destructive processes such as atherosclerosis, hypertension, diabetic complications, (re)stenosis, and tissue infarction, as well as the undermining of clinical therapy like in the case of nitrate tolerance. This review takes a focused look at key elements of the cGMP signaling cascade in vascular tissue, particularly recent advances in our knowledge of cGMP-dependent protein kinase (cGK, also known as PKG) function. Finally, we discuss the potential of clinical monitoring of cGK activity for assessing the functional status of cGMP signaling and for guiding the design of therapeutic strategies to improve vascular function.
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cGMP Synthesis |
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One of the 2 major synthetic pathways for cGMP generation from guanosine 5'-triphosphate (GTP) is directed by NPs (Figure 1), consisting of atrial (ANP), B-type (BNP), and C-type
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|
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