Revealing the polarity decrease of cardiomyocyte in the septic cardiomyopathy by a lipid droplets-targeting...

Area of Science:

• Cardiology
• Biochemistry
• Molecular Biology

Background:

• Septic cardiomyopathy (SCM) is a primary cause of mortality in sepsis patients, with underlying pathogenic mechanisms still under investigation.
• Lipid droplets (LDs) play a crucial role in cellular lipid metabolism, and their abnormal aggregation and polarity are implicated in cardiac diseases.
• Current methods lack the ability to visualize altered LD polarity specifically in SCM models.

Purpose of the Study:

• To design and synthesize a novel polarity-sensitive fluorescent probe for visualizing LD polarity.
• To investigate the role of LD polarity changes in the pathogenesis of SCM.
• To establish a reliable tool for studying SCM mechanisms and potential therapeutic targets.

Main Methods:

• Synthesis of a donor-π-acceptor (D-π-A) based polarity-sensitive probe, BDP-551.
• Characterization of BDP-551 for photostability, LD targeting, and near-infrared (NIR) emission.
• Application of BDP-551 with confocal imaging microscopy in SCM model cells, zebrafish, and mouse hearts.

Main Results:

• BDP-551 demonstrated excellent photostability, high LD targeting, NIR emission (678 nm), and strong polarity sensitivity.
• The probe successfully detected polarity changes in SCM model cells and visualized LDs in hypoxic/inflamed zebrafish.
• BDP-551 revealed a decrease in microenvironmental polarity in mouse hearts affected by SCM.

Conclusions:

• BDP-551 is a robust tool for visualizing microenvironmental polarity fluctuations in SCM.
• The findings provide new insights into the pathogenic mechanisms of SCM related to LD polarity.
• This probe can facilitate further research into therapeutic strategies for SCM.