1
40
1
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1073/pnas.0408704102" target="_blank" rel="noreferrer noopener">http://doi.org/10.1073/pnas.0408704102</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
437-442
Issue
2
Volume
102
Search for Full-text
Locate full-text within NEOMED Library's e-journal collections
<p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p>
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase
Publisher
An entity responsible for making the resource available
Proceedings of the National Academy of Sciences of the United States of America
Date
A point or period of time associated with an event in the lifecycle of the resource
2005
2005-01
Subject
The topic of the resource
adrenomedullin; angiotensin-ii; cardiac fibroblast; cyclic AMP; extracellular-matrix; failure; fibrosis; gene-expression; growth-factor-beta; heart; lung fibroblasts; modulation; necrosis-factor-alpha; phenotypic; rat ventricular myocytes; Science & Technology - Other Topics; smooth muscle actin
Creator
An entity primarily responsible for making the resource
Swaney J S; Roth D M; Olson E R; Naugle J E; Meszaros J G; Insel P A
Description
An account of the resource
Transformation of fibroblasts to myofibroblasts, characterized by expression of alpha-smooth muscle actin (alpha-SMA) and production of extracellular matrix (ECM) components, is a key event in connective tissue remodeling. Approaches to inhibit this transformation are needed in tissues, such as the heart, where excessive ECM production by cardiac fibroblasts (CFs) causes fibrosis, myocardial stiffening, and cardiac dysfunction. We tested whether adenylyl cyclase (AC) activation (increased cAMP levels) modulates the transformation of adult rat CF to myofibroblasts, as assessed by immunofluorescent microscopy, immunoblotting, and collagen synthesis. A 24-h incubation of CF with TGF-beta or angiotensin II increased alpha-SMA expression, which was inhibited by the AC agonist forskolin and a cAMP analog that activates protein kinase A. Treatment with forskolin blunted serum-, TGF-beta-, and angiotensin II-stimulated collagen synthesis. CFs engineered to overexpress type 6 AC had enhanced forskolin-promoted cAMP formation, greater inhibition by forskolin of TGF-beta-stimulated alpha-SMA expression, and a decrease in the EC50 of forskolin to reduce serum-stimulated collagen synthesis. The AC stimulatory agonist adrenomedullin inhibited collagen synthesis in CF that overexpressed AC6 but not in controls. Thus, AC stimulation blunts collagen synthesis and, in parallel, the transformation of adult rat CF to myofibroblasts. AC overexpression enhances these effects, "uncovering" an inhibition by adrenomedullin. These findings implicate cAMP as an inhibitor of ECM formation by means of blockade of the transformation of CF to myofibroblasts and suggest that increasing AC expression, thereby enhancing cAMP generation through stimulation of receptors expressed on CF, could provide a means to attenuate and prevent cardiac fibrosis and its sequelae.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1073/pnas.0408704102" target="_blank" rel="noreferrer noopener">10.1073/pnas.0408704102</a>
Format
The file format, physical medium, or dimensions of the resource
Journal Article
2005
adrenomedullin
angiotensin-ii
cardiac fibroblast
cyclic AMP
extracellular-matrix
failure
Fibrosis
gene-expression
growth-factor-beta
heart
Insel P A
Journal Article
lung fibroblasts
Meszaros J G
modulation
Naugle J E
necrosis-factor-alpha
Olson E R
phenotypic
Proceedings of the National Academy of Sciences of the United States of America
rat ventricular myocytes
Roth D M
Science & Technology - Other Topics
smooth muscle actin
Swaney J S