Search: onr:"swepub:oai:prod.swepub.kib.ki.se:147395994" >
Nitro-Oleic Acid (N...
Nitro-Oleic Acid (NO2-OA) Improves Systolic Function in Dilated Cardiomyopathy by Attenuating Myocardial Fibrosis
-
Braumann, S (author)
-
Schumacher, W (author)
-
Im, NG (author)
-
show more...
-
Nettersheim, FS (author)
-
Mehrkens, D (author)
-
Bokredenghel, S (author)
-
Hof, A (author)
-
Nies, RJ (author)
-
Adler, C (author)
-
Winkels, H (author)
-
Knoll, R (author)
-
Freeman, BA (author)
-
Rudolph, V (author)
-
Klinke, A (author)
-
Adam, M (author)
-
Baldus, S (author)
-
Mollenhauer, M (author)
-
Geissen, S (author)
-
show less...
- 2021-08-22
- 2021
- English.
-
In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:16
- Related links:
-
https://doi.org/10.3...
-
show more...
-
http://kipublication...
-
https://doi.org/10.3...
-
show less...
Abstract
Subject headings
Close
- Nitro-oleic acid (NO2-OA), a nitric oxide (NO)- and nitrite (NO2−)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp−/−) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO2-OA on cardiac function in Mlp−/− mice both in vivo and in vitro. Mlp−/− mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp−/− mice exhibited enhanced TGFβ signalling, fibrosis and severely reduced left ventricular systolic function. NO2-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp−/− mice. In vitro studies of TGFβ-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO2-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFβ downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO2-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFβ signaling.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Braumann, S
-
Schumacher, W
-
Im, NG
-
Nettersheim, FS
-
Mehrkens, D
-
Bokredenghel, S
-
show more...
-
Hof, A
-
Nies, RJ
-
Adler, C
-
Winkels, H
-
Knoll, R
-
Freeman, BA
-
Rudolph, V
-
Klinke, A
-
Adam, M
-
Baldus, S
-
Mollenhauer, M
-
Geissen, S
-
show less...
- Articles in the publication
-
International jo ...
- By the university
-
Karolinska Institutet