Deficiency in Heat Shock Factor 1 (HSF-1) Expression Exacerbates Sepsis-induced Inflammation and Cardiac Dysfunction

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Biology

Background:

• Sepsis can lead to severe cardiac dysfunction.
• The role of heat shock factor 1 (HSF-1) in sepsis-induced myocardial injury is not fully understood.
• Heat shock proteins (HSPs) are known to protect cells from stress.

Purpose of the Study:

• To investigate the impact of HSF-1 absence on inflammatory cytokine production and myocardial contractility during sepsis.
• To determine if HSF-1 deficiency alters the cardiac response to sterile (LPS) and infectious (Streptococcus pneumoniae, Klebsiella pneumoniae) septic challenges.

Main Methods:

• Utilized HSF-1 knockout (hsf-/-) and wild-type littermate mice.
• Administered sterile (lipopolysaccharide; LPS) or infectious (Streptococcus pneumoniae or Klebsiella pneumoniae) septic challenges.
• Measured blood and cardiomyocyte cytokine production (TNF, IL-1β, IL-6, IL-10).
• Assessed myocardial contractility and intracellular ion responses in isolated cardiomyocytes.

Main Results:

• HSF-1 knockout mice exhibited exaggerated production of inflammatory cytokines (TNF, IL-1β, IL-6, IL-10) in blood and cardiomyocytes compared to wild-type mice.
• This enhanced myocardial inflammation in hsf-/- mice was associated with significantly decreased cardiac contraction and relaxation.
• Intracellular calcium and sodium levels in cardiomyocytes were not significantly affected by HSF-1 deficiency during sepsis, suggesting ion loading is not the primary cause of contractile defects.

Conclusions:

• HSF-1 and its downstream heat shock proteins are essential for supporting cardiac function during sepsis.
• Absence of HSF-1 leads to increased myocardial inflammation and impaired cardiac contractility in a sepsis model.
• Further research is needed to elucidate the precise mechanisms of HSF-1-mediated cardiac protection in sepsis.