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Cardioprotection and Mitochondrial Signaling: Insights from Molecular Mechanisms to Therapeutic Strategies

Special Issue Editor


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Guest Editor
Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Mexico
Interests: cardioprotection; kinase signaling; mitochondria; caveolae; bioenergetics

Special Issue Information

Dear Colleagues,

Mitochondrial dysfunction is a key feature of ischemia/reperfusion damage, as well as heart failure, both the leading causes of death and disability worldwide. Therefore, cardioprotective strategies to prevent alterations of the function of these organelles are currently directed toward reducing the formation of reactive oxygen species, inhibiting the opening of the mitochondrial permeability transition pore, regulating kinase signaling and maintaining mitochondrial quality control.

This Special Issue will publish original articles focused on mitochondria as a therapeutic target and novel forms of cardioprotection with the potential to be translated to clinical settings for improving outcomes in AMI patients and preventing heart failure.

All submissions will be peer-reviewed, following the same evaluation criteria as individual IJMS submissions.

Dr. Cecilia Zazueta
Guest Editor

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Keywords

  • cardioprotection
  • mitochondrial signaling
  • mitochondrial dysfunction
  • heart failure
  • ischemia/reperfusion
  • mitochondria
  • reactive oxygen species

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Published Papers (1 paper)

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Research

21 pages, 4383 KiB  
Article
Pharmacologic ROMK Inhibition Protects Against Myocardial Ischemia Reperfusion Injury
by Allison C. Wexler, Holly Dooge, Lara Serban, Aditya Tewari, Babak M. Tehrani, Francisco J. Alvarado and Mohun Ramratnam
Int. J. Mol. Sci. 2025, 26(8), 3795; https://doi.org/10.3390/ijms26083795 - 17 Apr 2025
Viewed by 139
Abstract
Mitochondrial ATP-sensitive K+ channels are closely linked to cardioprotection and are potential therapeutic targets during ischemia reperfusion (IR) injury. The renal outer medullary K+ channel isoform 2 (ROMK2) is an ATP-sensitive K+ channel found in the mitochondria of cardiomyocytes. While the germline knockout [...] Read more.
Mitochondrial ATP-sensitive K+ channels are closely linked to cardioprotection and are potential therapeutic targets during ischemia reperfusion (IR) injury. The renal outer medullary K+ channel isoform 2 (ROMK2) is an ATP-sensitive K+ channel found in the mitochondria of cardiomyocytes. While the germline knockout of ROMK does not mediate myocardial IR injury, the effect of ROMK loss of function on IR injury in the adult myocardium is unknown. By using a selective small molecule inhibitor of ROMK, we paradoxically found that mouse hearts were protected from IR injury after ROMK inhibition compared to vehicle-treated animals. In addition, we found that ROMK inhibition leads to exaggerated mitochondrial uncoupling and increased ROS production. Phosphatidylinositol 4,5-bisphosphate (PIP2), an activator of ROMK, increased the effect of ATP to hyperpolarize cardiac mitochondrial membrane potential. ROMK inhibition also increased mitochondrial swelling in the absence of ATP. In conclusion, pharmacologic ROMK inhibition protects the murine heart from IR injury and may promote a phenotype of enhanced mitochondrial matrix K+. ROMK may be more important during conditions that promote mitochondrial matrix K+ efflux than influx. Further research to understand its role in mitochondrial K+ handling and as a therapeutic target in IR injury is needed. Full article
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