The case for inhibiting p38 mitogen-activated protein kinase in heart failure

Area of Science:

• Cardiology
• Molecular Biology
• Pharmacology

Background:

• p38 mitogen-activated protein kinases (p38 MAPKs) are implicated in myocardial infarction and acute coronary syndromes.
• Evidence suggests p38 MAPKs are activated in the failing human heart and in animal models of heart failure.
• Chronic activation of stress pathways, including p38 MAPKs, is a feature of heart failure.

Purpose of the Study:

• To review the evidence supporting the therapeutic potential of p38 MAPK inhibition in heart failure.
• To compare the chronic activation of p38 MAPKs in heart failure to other established therapeutic pathways.
• To question the potential synergistic benefits of inhibiting p38 MAPKs.

Main Methods:

• Literature review of experimental studies and clinical trials.
• Analysis of evidence for p38 MAPK activation in human and animal models of heart failure.
• Philosophical comparison of stress pathway activation in heart failure.

Main Results:

• p38 MAPKs are activated in the myocardium of failing human hearts.
• p38 MAPKs are activated in the heart and blood vessels of animal models of heart failure.
• Chronic activation of adaptive stress pathways is analogous to established heart failure therapies.

Conclusions:

• Inhibition of p38 MAPKs shows potential therapeutic value in heart failure.
• The chronic activation of p38 MAPKs in heart failure mirrors other successful therapeutic targets.
• Further investigation is warranted to explore synergistic benefits of p38 MAPK inhibition.