AMP-Activated Protein Kinase Signaling in Cardiovascular Health

AMP-activated protein kinase (AMPK) serves as a central regulator of energy balance in cardiac and vascular cells, responding to fluctuations in cellular ATP levels by phosphorylating downstream targets that govern metabolism, growth and survival pathways. In the heart, AMPK activation limits pathological hypertrophy by inhibiting the mammalian target of rapamycin (mTOR) pathway and by modulating protein synthesis via eukaryotic elongation factor-2 kinase (eEF2K). In endothelial cells, AMPK phosphorylates endothelial nitric oxide synthase (eNOS), enhancing nitric oxide (NO) production and promoting vasodilatation, angiogenesis and an anti-inflammatory environment. In vascular smooth muscle cells, AMPK modulates phenotypic switching, reducing contractile dysfunction in ischaemic settings. Beyond acute stress responses, sustained AMPK activation contributes to antifibrotic effects, stabilises mitochondrial function and augments antioxidant defences, mediating cardioprotection during pressure overload, myocardial infarction and metabolic syndrome. Pharmacological activators and lifestyle interventions such as exercise harness these pleiotropic benefits, positioning AMPK as a therapeutic node in diverse cardiovascular disorders.

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AMP-Activated Protein Kinase Signaling in Cardiovascular Health publication trend

The graph below shows the total number of articles in amp-activated protein kinase signaling in cardiovascular health across all publications each year (not limited to Nature Index journals).

Technical terms

AMP-activated protein kinase (AMPK): A heterotrimeric serine/threonine kinase that senses cellular energy status via AMP/ATP binding and mediates adaptive metabolic and growth responses.

S-nitrosylation: A post-translational modification in which a nitric oxide (NO) moiety is covalently attached to a cysteine thiol, altering protein function.

Endothelial nitric oxide synthase (eNOS): An enzyme in vascular endothelium that produces NO, promoting vasodilatation and inhibiting platelet aggregation and inflammation.

Cardiac hypertrophy: An increase in cardiomyocyte size and protein synthesis, often driven by neurohormonal or mechanical stimuli, which may progress to maladaptive remodelling.

References

1. S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming. EMBO Reports (2023).
2. Sexual Dimorphism in Cardiometabolic Diseases: The Role of AMPK. International Journal of Molecular Sciences (2023).
3. AMPK: Regulating Energy Balance at the Cellular and Whole Body Levels. Physiology (2014).
4. Direct Activation of AMP-activated Protein Kinase Stimulates Nitric-oxide Synthesis in Human Aortic Endothelial Cells*. Journal of Biological Chemistry (2003).
5. Activation of AMP-activated Protein Kinase Inhibits Protein Synthesis Associated with Hypertrophy in the Cardiac Myocyte*. Journal of Biological Chemistry (2004).
6. AMP-activated Protein Kinase (AMPK) Signaling in Endothelial Cells Is Essential for Angiogenesis in Response to Hypoxic Stress*. Journal of Biological Chemistry (2003).
7. AMPK: a therapeutic target of heart failure - not only metabolism regulation. Bioscience Reports (2019).
8. Cardiac Fibrosis Alleviated by Exercise Training Is AMPK-Dependent. PLOS ONE (2015).
9. AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. Journal of Molecular and Cellular Cardiology (2013).