Notch3 may reduce heart scarring after a heart attack by blocking the TGF-β1/Smad3 signaling pathway

Notch3 cDNA treatment attenuated cardiac damage and inhibited fibrosis in mice with myocardial infarction.

• Notch3 signaling is associated with reduced cardiac fibrosis and improved cardiac function following myocardial infarction.
• Administration of Notch3 siRNA worsened cardiac damage and increased fibrosis in the same model.
• Notch3 overexpression inhibited the transition of cardiac fibroblasts to myofibroblasts induced by TGF-β1.
• Key fibrotic proteins, including a-smooth muscle actin and Type I collagen, were down-regulated with Notch3 overexpression in cardiac fibroblast cells.
• Notch3 treatment led to increased levels of MMP-9 and decreased levels of TIMP-2 in TGF-β1-stimulated cardiac fibroblasts.

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