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Rap1GAP exacerbates myocardial infarction by regulating the AMPK/SIRT1/NF-κB signaling pathway

Tiantian Shan1, Xiaoying Li2, Wenzhi Xie3

  • 1Department of Cardiology, Jinan Central Hospital, Shandong University, Jinan 250013, China; Research Center of Translational Medicine, Central Hospital Affiliated Shandong First Medical University, Jinan 250013, China.

Cellular Signalling
|February 6, 2024
PubMed

Insights

Rap1 GTPase-activating protein (Rap1GAP) worsens myocardial infarction (MI) by inhibiting the AMPK/SIRT1 pathway and activating NF-κB. Reducing Rap1GAP protects the heart from MI damage, suggesting it as a therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Signaling

Background:

  • Rap1 GTPase-activating protein (Rap1GAP) is a known tumor suppressor.
  • The role of Rap1GAP in myocardial infarction (MI) and its underlying mechanisms remain largely unexplored.

Purpose of the Study:

  • To investigate the role of Rap1GAP in myocardial infarction (MI).
  • To elucidate the molecular mechanisms by which Rap1GAP influences MI progression.

Main Methods:

  • Cardiac-specific Rap1GAP conditional knockout (Rap1GAP-CKO) mice underwent myocardial infarction induction.
  • Transcriptome sequencing and Gene Set Enrichment Analysis (GSEA) were performed on heart tissues.
  • Primary rat myocardial cells were subjected to oxygen-glucose deprivation (OGD) to mimic ischemia and hypoxia.

Main Results:

  • Rap1GAP expression increased post-MI, correlating with increased apoptosis, inflammation, infarct size, and cardiac dysfunction.
  • Rap1GAP-CKO mice showed alleviated cardiac damage.
  • Rap1GAP was found to inhibit the AMPK/SIRT1 pathway and activate the NF-κB signaling pathway, exacerbating ischemia-reperfusion injury.
  • Activating AMPK with AICAR reversed Rap1GAP-induced cardiomyocyte damage.

Conclusions:

  • Rap1GAP promotes myocardial infarction by modulating the AMPK/SIRT1/NF-κB signaling pathway.
  • Rap1GAP may represent a potential therapeutic target for treating myocardial infarction.
Keywords:
AMPK/SIRT1/NF-κB signaling pathwayApoptosisInflammationMyocardial infarctionOxidative stressRap1GAP

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