Journal: Physiological Reports
Article Title: Dapagliflozin prevents ERK activation and SGLT2‐dependent endoglin upregulation in a mechanically provoked cardiac injury model
doi: 10.14814/phy2.15990
Figure Lengend Snippet: Proposed mechanism for Dapagliflozin on troponin I, endoglin (CD105) and ERK activation in the mechanically injured cardiac cell model. Our model depicts the upregulation of troponin I and endoglin (CD105) after mechanically triggered cardiac injury. (a) Cardiomyocytes were seeded on stretchable PDMS membrane, subjected to cyclic stretch at 5% and 25% elongation. After cyclic stretch, troponin I and CD105 were increased, triggering downstream p‐ERK to enter cell nucleus, potentially altered gene transcription that promoted upregulation of p‐eNOS. The accumulated p‐ERK nuclear translocation and p‐eNOS activation led to an imbalanced regulation of sodium/calcium ions. Finally, the cardiomyocytes were overwhelmed by loss of sodium/calcium ions homeostasis, renting the cells susceptible to CVD‐related risk factor. (b) Dapagliflozin (DAPA), the inhibitor having higher affinity for SGLT2, is able to prevent the characteristics of the mechanically provoked biomarkers for cardiac injury. As a result, SGLT2 and/or SGLT1 is crucial in maintaining the normal function of cardiomyocytes.
Article Snippet: To analyze CD105 and TGF‐β level, the human CD105 ELISA kit (Boster Biological Technology, CatEK0644) and human TGF‐β assay ELISA kit (Boster Biological Technology, CatEK0513) were used to detect CD105 and TGF‐β level, respectively, in the collected serum.
Techniques: Activation Assay, Membrane, Translocation Assay