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Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
CD14-deficient mice are protected against lipopolysaccharide-induced cardiac inflammation and left ventricular
Pascal Knuefermann1, Shintaro Nemoto, Arunima Misra
1Department of Medicine, Baylor College of Medicine, Houston, Tex, USA.
Insights
CD14 is crucial for sepsis-induced heart dysfunction. Blocking CD14 in mice prevented cardiac issues and inflammation caused by lipopolysaccharide (LPS), highlighting CD14 as a therapeutic target for sepsis.
Area of Science:
- Cardiovascular Biology
- Immunology
- Molecular Medicine
Background:
- Sepsis-induced myocardial dysfunction mechanisms are unclear.
- CD14 mediates inflammatory responses to lipopolysaccharide (LPS) in organs, including the heart.
Purpose of the Study:
- To investigate the role of CD14 in lipopolysaccharide (LPS)-induced myocardial dysfunction in vivo.
Main Methods:
- Wild-type and CD14-deficient mice were challenged with Escherichia coli LPS.
- Cardiac function was assessed using echocardiography.
- Myocardial inflammatory markers (TNF, IL-1beta, NOS2) and NF-kappaB activation were measured.
Main Results:
- LPS increased myocardial TNF and IL-1beta in wild-type mice but not in CD14-deficient mice.
- NOS2 induction and NF-kappaB activation were observed in wild-type mice post-LPS, but not in CD14-deficient mice.
- LPS impaired cardiac function in wild-type mice, while CD14-deficient mice maintained normal cardiac function.
Conclusions:
- CD14 plays a key role in mediating the cardiac inflammatory response to LPS.
- CD14 is essential for the development of left ventricular dysfunction during LPS-induced shock.
Background:
The molecular mechanisms responsible for sepsis-induced myocardial dysfunction remain undefined. CD14 mediates the inflammatory response to lipopolysaccharide (LPS) in various organs including the heart. In this study we investigated the role of CD14 in LPS-induced myocardial dysfunction in vivo.
Methods And Results:
Wild-type and CD14-deficient (CD14-D) mice were challenged with Escherichia coli LPS. Myocardial tumor necrosis factor, interleukin-1beta (IL-1beta), and NOS2 induction was measured before and 6 hours after LPS challenge. Echocardiographic parameters of left ventricular function were measured before and 6 hours after LPS administration. LPS challenge induced a significant increase in myocardial tumor necrosis factor and IL-1beta mRNA and protein expression in wild-type mice. In contrast, mRNA and protein levels for TNF and IL-1beta were significantly blunted in CD14-D mice. An increase in NOS2 protein was noted within 6 hours of LPS provocation only in the hearts of wild-type mice. This was associated with an increase in ventricular cGMP levels. Activation of nuclear factor-kappaB was observed within 30 minutes of LPS in the hearts of wild-type mice but not in CD14-D mice. In wild-type mice, LPS significantly decreased left ventricular fractional shortening, velocity of circumferential shortening, and dP/dt(max). LPS-treated CD14-D mice maintained normal cardiac function.
Conclusions:
These results suggest that CD14 is important in mediating the proinflammatory response induced by LPS in the heart and that CD14 is necessary for the development of left ventricular dysfunction during LPS-induced shock in vivo.
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