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. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This study successfully developed two fluorescent turn-on probes (KXS-M1 and KXS-M2) for the highly selective and sensitive detection of monoamine oxidase A (MAO-A). Among them, KXS-M2 exhibited better fluorescence increment and sensitivity, and can be used for the diagnosis and treatment of heart failure.