Ca2+/Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression...

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Inflammation is a key factor in cardiovascular disease (CVD) development.
• The immune system presents a therapeutic target for CVD treatment.
• Toll-like receptor (TLR) stimulation influences inflammatory responses and cardiac function.

Purpose of the Study:

• To investigate the mechanisms of inflammatory response and cardiomyocyte hypertrophy induced by TLR agonists (LPS and HSP60).
• To evaluate the role of Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) in these processes.
• To determine the effect of CaMKIIδB silencing on TLR-induced inflammation and hypertrophy.

Main Methods:

• Utilized bacterial lipopolysaccharide (LPS) and heat shock protein 60 (HSP60) to stimulate Toll-like receptors (TLRs) in cardiomyocytes.
• Employed in vitro silencing of CaMKIIδB using small interfering RNA (siRNA).
• Assessed gene expression for complement system components (C3, factor B), inflammatory cytokines (IL-6, TNF-α), and nuclear factor-kappa B (NF-κB).

Main Results:

• LPS and HSP60 treatment induced cardiomyocyte hypertrophy and expression of complement genes C3 and factor B.
• CaMKIIδB silencing prevented complement gene transcription and hypertrophy linked to TLR 2/4 activation.
• CaMKIIδB silencing attenuated NF-κB expression but did not inhibit IL-6 and TNF-α increases.
• Extracellular HSP60 was shown to activate complement gene expression via CaMKIIδB.

Conclusions:

• CaMKIIδB acts as a crucial link between inflammation and cardiac hypertrophy.
• Extracellular HSP60 activates complement gene expression through CaMKIIδB.
• CaMKIIδB silencing mitigates LPS- or HSP60-induced cardiomyocyte hypertrophy, irrespective of the inflammatory response.