The Role of the Notch Signaling Pathway in Recovery of Cardiac Function after Myocardial Infarction

Figures

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  Figure 1. Tissue and cellular events in MI. After ischemic exposure, an increase in the level of ROS and the lack of ATP lead to cell death and a release of inflammatory mediators. During the inflammation stage, the following processes occur: phagocytosis of the dead cells’ debris and the formation of new capillaries. At the termination stage, some conditions for restoring the integrity of the myocardium by replacing dead CMC with fibroblasts and hypertrophy of surviving CMC occur. “Created with BioRender.com”.

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  Figure 2. Schematic representation of Notch signaling pathway. A Notch ligand (DLL or JAG) binds to the Notch receptor (Notch1-4). The Notch intracellular domain (NICD) is cleaved when binding the receptor, and activated NICD enters the nucleus, where it interacts with intracellular regulatory complexes, after which the transcription of Notch target genes begins. “Created with BioRender.com”.

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  Figure 3. The role of the Notch signaling pathway in reducing oxidative stress at CMC. The launch of the Notch signaling pathway enhances the synthesis of the Mfn2 protein responsible for mitophagy. The Notch1 receptor can bind to the tumor necrosis factor-α and block its action. The production of antioxidant enzymes is controlled through the Akt cascade. Energy conservation in the cell is achieved by activating the AMPK cascade. “Created with BioRender.com”.

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  Figure 4. The significance of the Notch signaling pathway in preventing CMC apoptosis. Through the transmission of the Notch signal, a decrease in the expression of pro-apoptotic Bax and an increase in the expression of anti-apoptotic Bcl-2 is achieved. Additionally, the prevention of apoptosis can be achieved by increasing the expression of genes associated with autophagy. Inhibition of the pro-apoptotic tumor necrosis factor-α also helps prevent apoptosis. “Created with BioRender.com”.

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  Figure 5. Effects of Notch pathway in inflammatory response. Notch signaling promotes the acquisition of a pro-inflammatory M1-macrophage phenotype that secretes inflammatory mediators.

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  Figure 6. The mechanism of inhibition of myocardial remodeling in fibroblasts. The intracellular domain of the Notch receptor (NICD) inhibits signal transmission along the TGFß-1/SMAD3 pathway due to competition for the α-SMA promoter. “Created with BioRender.com”.

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  Figure 7. Differences between normal and hypertrophied CMCs. Hypertrophied CMCs differ from normal CMCs in terms of electrochemical features and a longer period of vulnerability to extra contractions. This is due to a change in the amount and conductive properties of potential-dependent potassium channels.

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  Figure 8. The role of Notch in angiogenesis. VEGF triggers the expression of DLL4 ligands in a leading tip cell, triggering the Notch in adjacent stalk cells. The direction of migration of tip cells is determined by the CXCR4 chemokine receptors. “Created with BioRender.com”.