Specific tracking of monoamine oxidase A in heart failure models by a far-red fluorescent probe with an ultra large Stokes shift

Monoamine oxidase A (MAO-A) is a prominent myocardial source of reactive oxygen species (ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAO-A activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart failure. However, so far, there is no report on the fluorescent diagnosis of heart failure by a specific probe for MAO-A. In this work, two far-red emissive fluorescent turn-on probes (KXS-M1 and KXS-M2) for the highly selective and sensitive detection of MAO-A were fabricated. Both probes exhibit good response to MAO-A, one of which, KXS-M2, performs better than the other one in terms of a fluorescence increment and sensitivity. Using the pioneering probe KXS-M2, specific fluorescence imaging of MAO-A in glucose-deprived H9c2 cardiac cells, zebrafish and isoprenaline-induced failing heart tissues was achieved, proving that KXS-M2 can serve as a powerful tool for the diagnosis and treatment of heart failure. MAO-A is an outer mitochondrial membrane-located enzyme, which not only catalyzes the oxidative deamination of serotonin (5-HT) and norepinephrine (NE) in the heart, but also produces H2O2 and relative aldehydes as by-products during the degradation process. Enhanced MAO-A activity contributes to cardiac dysfunction and heart failure. For specific monitoring of MAO-A activity in heart failure, we developed a novel dicyanoisophorone-based far-red fluorescent probe KXS-M2 with an ultra large Stokes shift. Utilizing KXS-M2, fluorescence imaging of MAO-A in heart failure mouse model was achieved. [Display omitted]