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Hexokinase 2-Driven Cardioprotection in Ischemia, Hypertrophy, and Regeneration: From Underlying Mechanisms to

Junying Gao1,2, Jun Qi3, Zhaodi Zheng4

  • 1Key Laboratory of Evolution and Marine Biodiversity (Ministry of Education) and Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, China.

Biofactors (Oxford, England)
|February 11, 2026
PubMed

Insights

Hexokinase 2 (HK2) protects the heart during pathological conditions by enhancing glycolysis. Targeting the HK2-mitochondrial association offers potential therapeutic strategies for cardiac protection.

Area of Science:

  • Cardiology
  • Biochemistry
  • Molecular Biology

Background:

  • The heart is highly energy-dependent, relying mainly on oxidative phosphorylation, but shifts to glycolysis under stress.
  • Hexokinase 2 (HK2) is a key enzyme in glycolysis, increasingly recognized for its cardioprotective roles in disease.

Purpose of the Study:

  • To review the functions and molecular mechanisms of HK2 in cardiac ischemia/hypoxia, hypertrophy, and regeneration.
  • To discuss the therapeutic potential of targeting HK2 and its mitochondrial association in cardiac pathologies.

Main Methods:

  • Literature review summarizing existing research on HK2 in cardiac conditions.
  • Analysis of molecular mechanisms underlying HK2's protective effects.
  • Discussion of pharmacological targeting strategies and future research directions.

Main Results:

  • HK2 plays a crucial role in enhancing cardiac glycolysis under pathological conditions.
  • HK2 confers protection against ischemia/hypoxia, hypertrophy, and aids in cardiac regeneration.
  • The association of HK2 with mitochondria is a key aspect of its function and therapeutic potential.

Conclusions:

  • HK2 is a vital protective factor in the stressed heart, primarily through modulating glycolysis.
  • Targeting HK2, particularly its mitochondrial binding, presents a promising avenue for developing novel cardioprotective therapies.
  • Further research into HK2-mitochondrial interactions can unlock new therapeutic strategies for heart disease.

Keywords:
HK2cardiac hypertrophycardiac ischemiacardiac regenerationdrugs

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