Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform

Area of Science:

• Cardiology
• Physiology
• Molecular Biology

Background:

• Remote preconditioning (RPC) is a phenomenon where brief ischemia-reperfusion of remote organs protects the heart.
• The intracellular mechanisms underlying RPC, particularly its role in myocardial protection, remain largely unknown.
• Protein kinase C epsilon (PKCepsilon) is a known mediator of classical ischemic preconditioning.

Purpose of the Study:

• To test the hypothesis that RPC activates myocardial PKCepsilon.
• To investigate the mechanisms of RPC signal transduction to the heart.
• To explore the potential contribution of kinins and neuronal reflexes in RPC.

Main Methods:

• Anesthetized rats underwent RPC (mesenteric artery occlusion/reperfusion) or served as controls.
• Myocardial infarct size was assessed after coronary artery occlusion and reperfusion.
• PKCepsilon translocation, bradykinin B(2) receptor antagonism (HOE140), and ganglion blockade (hexamethonium) were evaluated.

Main Results:

• RPC significantly reduced myocardial infarct size, an effect blocked by a PKC inhibitor.
• RPC induced PKCepsilon translocation, indicating activation, which was abolished by HOE140.
• Ganglion blockade prevented RPC-induced PKCepsilon activation.

Conclusions:

• RPC activates myocardial PKCepsilon via a pathway involving neuronal signaling and bradykinin.
• PKCepsilon activation is a key mechanism in the cardioprotection afforded by RPC.
• This study elucidates the molecular underpinnings of remote preconditioning.