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Nitro-Oleic Acid (N...
Nitro-Oleic Acid (NO2-OA) Improves Systolic Function in Dilated Cardiomyopathy by Attenuating Myocardial Fibrosis
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Braumann, S (författare)
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Schumacher, W (författare)
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Im, NG (författare)
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Nettersheim, FS (författare)
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Mehrkens, D (författare)
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Bokredenghel, S (författare)
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Hof, A (författare)
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Nies, RJ (författare)
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Adler, C (författare)
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Winkels, H (författare)
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Knoll, R (författare)
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Freeman, BA (författare)
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Rudolph, V (författare)
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Klinke, A (författare)
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Adam, M (författare)
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Baldus, S (författare)
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Mollenhauer, M (författare)
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Geissen, S (författare)
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- 2021-08-22
- 2021
- Engelska.
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:16
- Relaterad länk:
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https://doi.org/10.3...
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http://kipublication...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
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- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Braumann, S
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Schumacher, W
-
Im, NG
-
Nettersheim, FS
-
Mehrkens, D
-
Bokredenghel, S
-
visa fler...
-
Hof, A
-
Nies, RJ
-
Adler, C
-
Winkels, H
-
Knoll, R
-
Freeman, BA
-
Rudolph, V
-
Klinke, A
-
Adam, M
-
Baldus, S
-
Mollenhauer, M
-
Geissen, S
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visa färre...
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Karolinska Institutet