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Updated: Aug 14, 2026
A Modified Simple Method for Induction of Myocardial Infarction in Mice
Published on: December 3, 2021
H11 kinase prevents myocardial infarction by preemptive preconditioning of the heart
Christophe Depre1, Li Wang, Xiangzhen Sui
1Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, Medical School, Newark, NJ 07103, USA. deprech@umdnj.edu
Insights
H11 kinase (H11K) activation in the heart mimics ischemic preconditioning, significantly reducing heart attack size. This sustained activation of survival pathways offers a novel cardioprotection strategy for ischemic heart disease patients.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Ischemic Heart Disease Research
Background:
- Ischemic preconditioning protects the heart but has transient effects and is difficult to apply clinically.
- Sustained activation of preconditioning mechanisms is a novel cardioprotection strategy.
- H11 kinase (H11K) is elevated in chronic ischemic heart disease and ischemia models.
Purpose of the Study:
- To investigate the role of H11 kinase (H11K) in cardioprotection.
- To determine if H11K activation can mimic ischemic preconditioning effects.
- To elucidate the molecular mechanisms by which H11K confers protection.
Main Methods:
- Generated transgenic (TG) mice with increased cardiac H11K expression.
- Subjected TG and wild-type (WT) mice to coronary artery occlusion and reperfusion.
- Analyzed infarct size, survival kinase activation (Akt, AMPK), protein interactions, and downstream signaling pathways.
Main Results:
- TG mice exhibited an 82% reduction in infarct size, comparable to WT mice undergoing ischemic preconditioning (84% reduction).
- H11K activated survival kinases Akt and AMPK, promoting their nuclear translocation and complex formation.
- H11K modulated pro- and anti-apoptotic factors, increased HIF-1alpha, and shifted metabolism towards glucose utilization.
Conclusions:
- H11K activation preemptively triggers anti-apoptotic and metabolic responses to ischemia.
- H11K is sufficient to confer potent cardioprotection in vivo, mimicking ischemic preconditioning.
- Targeting H11K represents a promising therapeutic approach for ischemic heart disease.
Abstract:
Ischemic preconditioning confers powerful protection against myocardial infarction through pre-emptive activation of survival signaling pathways, but it remains difficult to apply to patients with ischemic heart disease, and its effects are transient. Promoting a sustained activation of preconditioning mechanisms in vivo would represent a novel approach of cardioprotection. We tested the role of the protein H11 kinase (H11K), which accumulates by 4- to 6-fold in myocardium of patients with chronic ischemic heart disease and in experimental models of ischemia. This increased expression was quantitatively reproduced in cardiac myocytes using a transgenic (TG) mouse model. After 45 minutes of coronary artery occlusion and reperfusion, hearts from TG mice showed an 82+/-5% reduction in infarct size compared with wild-type (WT), which was similar to the 84+/-4% reduction of infarct size observed in WT after a protocol of ischemic preconditioning. Hearts from TG mice showed significant activation of survival kinases participating in preconditioning, including Akt and the 5'AMP-activated protein kinase (AMPK). H11K directly binds to both Akt and AMPK and promotes their nuclear translocation and their association in a multiprotein complex, which results in a stimulation of survival mechanisms in cytosol and nucleus, including inhibition of proapoptotic effectors (glycogen synthase kinase-3beta, Bad, and Foxo), activation of antiapoptotic effectors (protein kinase Cepsilon, endothelial and inducible NO synthase isoforms, and heat shock protein 70), increased expression of the hypoxia-inducible factor-1alpha, and genomic switch to glucose utilization. Therefore, activation of survival pathways by H11K preemptively triggers the antiapoptotic and metabolic response to ischemia and is sufficient to confer cardioprotection in vivo equally potent to preconditioning.
