KIF13B Attenuates Sepsis-Induced Myocardial Dysfunction through the Stabilization of PLIN5

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Sepsis Research

Background:

• Sepsis-induced cardiac dysfunction (SICD) significantly contributes to sepsis mortality.
• The role of Kinesin family member 13B (KIF13B) in SICD is currently unknown.
• KIF13B is recognized for its protective effects in metabolic and cardiovascular diseases.

Purpose of the Study:

• To investigate the role of KIF13B in the pathogenesis of SICD.
• To elucidate the molecular mechanisms by which KIF13B influences cardiac function during sepsis.
• To explore KIF13B/PLIN5 axis as a potential therapeutic target for SICD.

Main Methods:

• Utilized wild-type and KIF13B knockout mouse models subjected to sepsis induction (lipopolysaccharide or cecal ligation and puncture).
• Employed lipopolysaccharide-treated neonatal rat cardiomyocytes to study cellular mechanisms.
• Administered cardiac-directed AAV9-PLIN5 gene therapy to KIF13B knockout mice with SICD.

Main Results:

• KIF13B expression was significantly downregulated in septic hearts and cardiomyocytes.
• KIF13B deficiency exacerbated SICD, leading to impaired cardiac function, increased mortality, lipid accumulation, fibrosis, and mitochondrial dysfunction.
• Loss of KIF13B enhanced lysosomal degradation of perilipin 5 (PLIN5), disrupting its mitochondrial localization and impairing lipid homeostasis.
• Cardiac-specific AAV9-PLIN5 gene therapy ameliorated cardiac dysfunction, reduced lipid accumulation, and mitigated oxidative stress in KIF13B-deficient septic mice.

Conclusions:

• KIF13B plays a critical protective role in sepsis-induced cardiac dysfunction.
• The KIF13B/PLIN5 axis is a key regulator of cardiac lipid metabolism and mitochondrial function during sepsis.
• Targeting the KIF13B/PLIN5 pathway offers a promising therapeutic strategy for treating SICD.