From: Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient
Model | Metformin (dose/ duration) | Key results and major findings | Interpretation | References | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Energy homeostasis | Oxidative stress | Intra-cellular Ca | Inflammation | Cx43 | EP changes | Cell structure | ||||
HL-1 atrial cells paced with 4 Hz (240 bpm) for 24 h | 1 mmol/L for 2 h | – | ↓ROS | – | – | – | – | ↑Cytoplasmic myosin heavy chain/nuclear area ratio ↑Troponin I | Metformin provided cardioprotection against AF-related adverse remodeling via attenuating tachy-induced myolysis and oxidative stress of atria cells | [44] |
Neonatal rat cardiomyocytes and HL-1 cell with field stimulation at 3 Hz for 12 h | 0.5 & 1 mmol/L | ↓cAMP→ ↓pSrc→ ↑AMPK→ ↑Cx43 | – | – | – | ↑ | ↑FPD | ↑ZO-1 | Metformin attenuated a shortened FPD possibly by improved gap junction function via AMPK activation, increased ZO-1 and Cx43 expression | [42] |
3T3-L1 mature adipocytes with LPS for 24 h then co-cultured with HL-1 atrial cell | 4 mmol/L incubated with adipocytes for 12 h | – | – | ↓Ca, ↑SERCA2a, ↑pPLN in HL-1 cell | ↑PPARγ/ APN, and ↓TNFα in adipocytes | – | – | – | Metformin improved Ca2+ homeostasis in HL-1 cell by attenuated the inflammatory interaction between adipocytes and HL-1 cell via an increased PPARγ/APN and suppressed TNFα | [45] |