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Updated: Jan 6, 2026
Technique of Minimally Invasive Transverse Aortic Constriction in Mice for Induction of Left Ventricular Hypertrophy
Published on: September 25, 2017
Dec1 Deficiency Suppresses Cardiac Perivascular Fibrosis Induced by Transverse Aortic Constriction
Hue Thi Le1,2, Fuyuki Sato3, Akira Kohsaka4
1Department of Physiology, Wakayama Medical University, Wakayama 641-8509, Japan. huele23989@gmail.com.
Insights
Mice lacking Differentiated embryonic chondrocyte gene 1 (Dec1) showed reduced cardiac fibrosis and preserved heart function after hypertrophic stress. Dec1 deficiency may offer a new therapeutic target for treating cardiac fibrosis.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Fibrosis Research
Background:
- Cardiac fibrosis contributes to cardiac dysfunction in hypertrophic hearts.
- The role of Differentiated embryonic chondrocyte gene 1 (Dec1), a heart-expressed transcription factor, in cardiac disease is unknown.
Purpose of the Study:
- To investigate the role of Dec1 in cardiac hypertrophy and fibrosis.
- To evaluate the therapeutic potential of targeting Dec1 in cardiac disease.
Main Methods:
- Utilized Dec1 knockout (Dec1KO) and wild-type (WT) mice subjected to transverse aortic constriction (TAC) or sham surgery.
- Assessed cardiac function, morphology, fibrosis markers, and Dec1 expression levels.
- Examined autopsy cases of myocardial hypertrophy and infarction.
Main Results:
- Dec1KO mice maintained cardiac function longer after TAC compared to WT mice.
- Dec1 deficiency suppressed cardiac perivascular fibrosis and associated molecular markers (S100A4, αSMA, TGFβ1, pSmad3, TNFα, p21).
- Dec1 expression increased in hypertrophic and infarcted human hearts, with disrupted circadian patterns in TAC-treated WT mice.
Conclusions:
- Dec1 deficiency mitigates cardiac fibrosis and preserves cardiac function in hypertrophic hearts.
- Dec1 plays a significant role in the development of cardiac fibrosis.
- Dec1 represents a potential therapeutic target for managing cardiac fibrosis.
Abstract:
Cardiac fibrosis is a major cause of cardiac dysfunction in hypertrophic hearts. Differentiated embryonic chondrocyte gene 1 (Dec1), a basic helix-loop-helix transcription factor, has circadian expression in the heart; however, its role in cardiac diseases remains unknown. Therefore, using Dec1 knock-out (Dec1KO) and wild-type (WT) mice, we evaluated cardiac function and morphology at one and four weeks after transverse aortic constriction (TAC) or sham surgery. We found that Dec1KO mice retained cardiac function until four weeks after TAC. Dec1KO mice also revealed more severely hypertrophic hearts than WT mice at four weeks after TAC, whereas no significant change was observed at one week. An increase in Dec1 expression was found in myocardial and stromal cells of TAC-treated WT mice. In addition, Dec1 circadian expression was disrupted in the heart of TAC-treated WT mice. Cardiac perivascular fibrosis was suppressed in TAC-treated Dec1KO mice, with positive immunostaining of S100 calcium binding protein A4 (S100A4), alpha smooth muscle actin (αSMA), transforming growth factor beta 1 (TGFβ1), phosphorylation of Smad family member 3 (pSmad3), tumor necrosis factor alpha (TNFα), and cyclin-interacting protein 1 (p21). Furthermore, Dec1 expression was increased in myocardial hypertrophy and myocardial infarction of autopsy cases. Taken together, our results indicate that Dec1 deficiency suppresses cardiac fibrosis, preserving cardiac function in hypertrophic hearts. We suggest that Dec1 could be a new therapeutic target in cardiac fibrosis.
