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Polarity-Tuned Lipid Droplet-Specific Probe for Heart Failure Imaging
Wenting Xu1, Caide Liu1, Wendi Cai1
1Affiliated Hospital of Shandong Second Medical University (261031, School of Clinical Medicine), School of Pharmacy, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China.
Insights
Researchers developed a new probe, WT-X, to detect changes in lipid droplets associated with heart failure (HF). This tool aids in visualizing abnormal lipid metabolism for better HF diagnosis and treatment monitoring.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Molecular Imaging
Background:
- Heart failure (HF) is a major cardiovascular disease with poor prognosis.
- Lipid droplet (LD) involvement in cardiovascular pathogenesis is increasingly recognized.
- Altered LD polarity disrupts lipid metabolism, contributing to HF development.
Purpose of the Study:
- To engineer and synthesize a novel polarity-sensitive probe for visualizing LD alterations in HF.
- To assess the probe's efficacy in detecting aberrant LD polarity in various HF models.
- To establish a tool for noninvasive monitoring of pathological lipid metabolism in HF.
Main Methods:
- Engineered and synthesized the BODIPY-based probe WT-X with a D-π-A framework.
- Evaluated WT-X for photostability, biocompatibility, and polarity selectivity.
- Applied WT-X to detect LD polarity changes in HF cardiomyocyte models, zebrafish, and mouse models.
Main Results:
- WT-X exhibited good photostability, biocompatibility, and high polarity selectivity.
- The probe successfully detected aberrant LD polarity alterations in HF models.
- Demonstrated sensitive visualization of pathological lipid metabolism in vivo.
Conclusions:
- WT-X is an effective tool for sensitive detection of aberrant LD polarity in HF.
- Facilitates noninvasive visualization of pathological lipid metabolism for precision HF management.
- Enables real-time monitoring of therapeutic efficacy and patient stratification in HF.
Abstract:
Heart failure (HF) is the ultimate development trend of most cardiovascular diseases, and a poor prognosis would result in serious consequences. Lately, the involvement of lipid droplets (LDs) in cardiovascular pathogenesis has garnered growing scientific recognition. Aberrant polarity alterations of LDs may destroy the balance of lipid metabolism, which is mechanistically linked to the occurrence and development of HF. In this investigation, we engineered and synthesized the probe WT-X utilizing the BODIPY scaffold, a polarity-sensitive molecular tool featuring a donor-π-acceptor (D-π-A) architectural framework, which exhibits good photostability, excellent biocompatibility, and high selectivity to polarity. WT-X demonstrated sensitive detection of aberrant lipid droplet polarity alterations in HF cardiomyocyte models, yolk sac region of inflamed live zebrafish, and the myocardial LDs in mice with HF. This discovery facilitates noninvasive visualization of pathological lipid metabolism for precision HF management, enabling real-time therapeutic efficacy monitoring and patient stratification.
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