JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

ACTIVATION OF KLOTHO/SIRT1 SIGNALING PATHWAY ATTENUATES MYOCARDIAL ISCHEMIA REPERFUSION INJURY IN DIABETIC RATS

  • 0Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Shock +

|

June 21, 2024

|

June 21, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Diabetic myocardial ischemia reperfusion (MIR) injury involves oxidative stress and impaired autophagy. Activating the Klotho/SIRT1 pathway with recombinant Klotho or SRT1720 reduces MIR injury in diabetic rats by lowering oxidative stress and restoring autophagy.

Area Of Science

  • Cardiovascular Biology
  • Metabolic Diseases
  • Cellular Signaling

Background

  • Diabetes mellitus and myocardial ischemia reperfusion (MIR) injury share common pathological features including oxidative stress, inflammation, and autophagy dysfunction.
  • Klotho and SIRT1 are key regulators of oxidative stress, influencing cellular processes like survival, aging, apoptosis, autophagy, and inflammation.
  • The protective role of the Klotho/SIRT1 pathway in the context of diabetic MIR injury remains to be fully elucidated.

Purpose Of The Study

  • To investigate the hypothesis that activating the Klotho/SIRT1 signaling pathway can attenuate myocardial ischemia reperfusion (MIR) injury in diabetic rats.
  • To examine the effects of recombinant Klotho (rKlotho) protein and a SIRT1 agonist (SRT1720) on diabetic MIR injury.
  • To elucidate the underlying mechanisms involving oxidative stress and autophagy modulation.

Main Methods

  • Established in vivo models of type 1 diabetes and MIR injury in rats.
  • Utilized in vitro models exposing primary rat cardiomyocytes and H9c2 cells to high glucose and hypoxia/reoxygenation (H/R).
  • Assessed hemodynamic parameters, infarct size, oxidative stress markers, cell viability, and Klotho/SIRT1 expression at mRNA and protein levels.

Main Results

  • Diabetic MIR hearts exhibited lower Klotho and SIRT1 expression, increased oxidative stress, and reduced autophagy compared to non-diabetic controls.
  • Administration of rKlotho protein and SRT1720 significantly attenuated MIR injury in diabetic rats.
  • Treatment with rKlotho and SRT1720 reduced oxidative stress and restored autophagy levels, indicating activation of the Klotho/SIRT1 pathway.

Conclusions

  • The Klotho/SIRT1 signaling pathway plays a critical role in mitigating myocardial ischemia reperfusion injury in the context of diabetes.
  • Recombinant Klotho protein and the SIRT1 agonist SRT1720 demonstrate therapeutic potential for alleviating diabetic myocardial IR injury.
  • Activation of the Klotho/SIRT1 pathway offers a promising strategy to reduce oxidative stress and restore autophagy in diabetic cardiovascular complications.