Detection of atherosclerosis-associated HOCl using a mitochondria-targeted fluorescent probe

Atherosclerosis is closely associated with cardiovascular and cerebrovascular diseases, which are the leading causes of death worldwide. The early diagnosis of atherosclerosis is helpful for prevention and treatment of related diseases. The formation of foam cells with upregulated HOCl level has been considered as a hallmark of the early atherosclerosis lesion. In this work, we reported a fluorescent probe AS-ClO for the detection of mitochondrial HOCl in foam cells for the first time. Upon reaction with HOCl, AS-ClO produced a dramatic fluorescence enhancement at 520 nm. The probe showed excellent selectivity toward HOCl with a low detection limit (12.53 nM) and a rapid response (within 5s). The mitochondria targetability of the probe was further confirmed by co-imaging test. The foam cells derived from MOVAS and RAW264.7 cells pre-treated with oxidized low-density lipoprotein exhibited 12.58-fold and 10.88-fold fluorescence enhancement with the help of the proposed probe, respectively. Moreover, a higher mitochondrial HOCl level in calcified MOVAS cells was imaged for the first time. Lastly, the over-production of HOCl in abdominal aorta sections from atherosclerotic mice was observed. The probe is anticipated to be used in the diagnosis of atherosclerosis and related diseases.

Automated summary

Atherosclerosis is closely related to cardiovascular and cerebrovascular diseases, being major causes of global mortality. Early diagnosis of atherosclerosis can aid in the prevention and treatment of associated diseases. A new fluorescent probe, AS-ClO, was developed for detecting mitochondrial HOCl in foam cells, showing high selectivity and sensitivity.