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

Lianxin Zhang; Guolin Miao; Si Mei; Yufei Han; Yitong Xu; Wenxi Zhang; Jingxuan Chen; Kaikai Lu; Yinqi Zhao; Zihao Zhou; Jinxuan Chen; Jiabao Guo; Pingping Lai; Sin Man Lam; Guanghou Shui; Ling Zhang; Weiguang Zhang; Wei Huang; Yuhui Wang; Xunde Xian

doi:10.34133/research.1033

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

Research (Wash D C). 2026 Jan 12:9:1033. doi: 10.34133/research.1033. eCollection 2026.

Authors

Lianxin Zhang¹, Guolin Miao^{1

2}, Si Mei¹, Yufei Han¹, Yitong Xu¹, Wenxi Zhang¹, Jingxuan Chen¹, Kaikai Lu¹, Yinqi Zhao¹, Zihao Zhou¹, Jinxuan Chen¹, Jiabao Guo¹, Pingping Lai¹, Sin Man Lam^{3

4}, Guanghou Shui³, Ling Zhang¹, Weiguang Zhang⁵, Wei Huang¹, Yuhui Wang¹, Xunde Xian^{1

5

6}

Affiliations

¹ Institute of Cardiovascular Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University, Beijing, China.
² Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
³ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
⁴ Lipidall Technologies Company Limited, Changzhou 213022, Jiangsu Province, China.
⁵ Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing, China.
⁶ Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University Third Hospital, Beijing, China.

Abstract

Sepsis-induced cardiac dysfunction (SICD) is a major contributor to mortality in sepsis. Kinesin family member 13B (KIF13B) has been identified as a critical protective factor for metabolic disorder and cardiovascular disease; however, the role of KIF13B in SICD remains unknown. After introducing lipopolysaccharide or cecal ligation and puncture surgery to wild-type (WT) and global Kif13b knockout (Kif13b ^-/-) mice combined with lipopolysaccharide-treated neonatal rat cardiomyocytes, we found that KIF13B expression levels were markedly down-regulated in septic hearts and cardiomyocytes. Kif13b deletion exacerbated SICD progress with reduced cardiac contractile function and resulted in increased mortality, accompanied by promoted lipid accumulation, fibrosis, and mitochondrial impairment. Mechanistically, the loss of KIF13B enhanced the lysosomal degradation of the lipid-droplet-associated protein perilipin 5 (PLIN5), thus disrupting the mitochondrial localization of PLIN5 and then impairing cardiac lipid homeostasis and proper mitochondrial function. Nevertheless, cardiac-directed AAV9-PLIN5 gene therapy sufficiently corrected cardiac dysfunction, inhibited lipid accumulation, and reduced oxidative stress in Kif13b ^-/- mice with SICD. In summary, these findings provide a new insight into the molecular mechanism underlying the pathogenesis of SICD, highlighting the KIF13B/PLIN5 axis as a potential therapeutic target for the treatment of SICD.