Cardiomyocyte Cell Cycle Activation Ameliorates Fibrosis in the Atrium

MHC-TGFcysser transgenic mice have elevated levels of active transforming growth factor (TGF)-β1 in the myocardium. Previous studies have shown that these animals develop atrial, but not ventricular, fibrosis. Here we show that atrial fibrosis was accompanied with cardiomyocyte apoptosis. Although s...

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Bibliographic Details
Published in:Circulation research 2006-01, Vol.98 (1), p.141-148
Main Authors: Nakajima, Hidehiro, Nakajima, Hisako O, Dembowsky, Klaus, Pasumarthi, Kishore B.S, Field, Loren J
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological and medical sciences
Cell Cycle
DNA - biosynthesis
Fibrosis
Fundamental and applied biological sciences. Psychology
Heart Atria - pathology
In Situ Nick-End Labeling
Mice
Mice, Inbred DBA
Mice, Transgenic
Myocytes, Cardiac - cytology
Signal Transduction
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - physiology
Transforming Growth Factor beta1
Vertebrates: cardiovascular system
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Summary:MHC-TGFcysser transgenic mice have elevated levels of active transforming growth factor (TGF)-β1 in the myocardium. Previous studies have shown that these animals develop atrial, but not ventricular, fibrosis. Here we show that atrial fibrosis was accompanied with cardiomyocyte apoptosis. Although similar levels of cardiomyocyte apoptosis were present in the right and left atria of MHC-TGFcysser hearts, the extent of fibrosis was more pronounced in the right atrium. Thus, additional factors influence the degree of atrial fibrosis in this model. Tritiated thymidine incorporation studies revealed cardiomyocyte cell cycle activity in left atrial cardiomyocytes, but not in right atrial cardiomyocytes. These observations suggested that cardiomyocyte cell cycle activation ameliorated the severity of atrial fibrosis. To directly test this hypothesis, MHC-TGFcysser mice were crossed with MHC-cycD2 mice (which have constitutive cardiomyocyte cell cycle activity in the right atrium). Mice inheriting both transgenes exhibited right atrial cardiomyocyte cell cycle activity and a concomitant reduction in the severity of right atrial fibrosis, despite the presence of a similar level of cardiomyocyte apoptosis as was observed in mice inheriting the MHC-TGFcysser transgene alone. These data support the notion that cardiomyocyte cell cycle induction can antagonize fibrosis in the myocardium.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.0000197783.70106.4a