Prediction of Early Atherosclerotic Plaques Using a Sequence‐Activated Fluorescence Probe for the Simultaneous Detection of γ‐Glutamyl Transpeptidase and Hypobromous Acid

Abstract

Atherosclerosis is a lipoprotein‐driven disease, and there is no effective therapy to reverse atherosclerosis or existing plaques. Therefore, it is urgently necessary to create a noninvasive and reliable approach for early atherosclerosis detection to prevent initial plaque formation. Atherosclerosis is intimately associated with inflammation, which is accompanied by an excess of reactive oxygen species (ROS), leading to cells requiring more glutathione (GSH) to resist severe oxidative stress. Therefore, the GSH‐hydrolyzed protein γ‐glutamyl transpeptidase (GGT) and the ROS‐hypobromous acid (HBrO) are potential biomarkers for predicting atherogenesis. Hence, to avoid false‐positive diagnoses caused by a single biomarker, we constructed an ingenious sequence‐activated double‐locked TP fluorescent probe, C‐HBrO‐GGT, in which two sequential triggers of GGT and HBrO are meticulously designed to ensure that the probe fluoresces in response to HBrO only after GGT hydrolyzes the probe. By utilization of C‐HBrO‐GGT, the voltage‐gated chloride channel (CLC‐1)‐HBrO‐catalase (CAT)‐GGT signaling pathway was confirmed in cellular level. Notably, the forthcoming atherosclerotic plaques were successfully predicted before the plaques could be observed via the naked eye or classical immunofluorescent staining. Collectively, this research proposed a powerful tool to indicate the precise position of mature plaques and provide early warning of atherosclerotic plaques.

γ-Gammaglutamyl transferase predicts all-cause mortality within three-year intervals in patients undergoing peritoneal dialysis

“…Increased γ-GGT activity indicates an insufficient antioxidant capacity and induces oxidative stress. Given its association with oxidative stress, γ-GGT has been recognized as a sensitive and reliable marker of cellular damage and stress response [ 14 , 15 ].Beyond its role in oxidative stress, γ-GGT has also been implicated in inflammatory processes, endothelial dysfunction, and atherosclerosis [ 6 , 16 , 17 ]. This association is particularly relevant in the context of PD, where chronic inflammation and oxidative stress are key factors contributing to the pathogenesis of associated comorbidities [ 2 ].…”

“…Nonetheless, it is yet unclear how γ-GGT affects prognosis in the dialysis population. Increased γ-GGT levels have been linked to CV risk, infection-related and all-cause mortality, as well as CV hospitalization in hemodialysis patients, according to a prior study [ 17 ]. In this retrospective study, we analyzed 640 PD patients from a single center and observed that in the two categories of γ-GGT median values across both sexes, those with lower levels of γ-GGT exhibited significantly lower all-cause and cardiovascular mortality rates at one, three, and five years.…”

In Situ Imaging of GGT and HOBr-Triggered Atherosclerotic Plaque Rupture via Activating the RunX2/Col IV Signaling Pathway

“…Recently, our group successfully developed a sequence-activated fluorescent probe for the detection of GGT and HOBr . However, the variations in emission channels of the probe following reaction with analytes were modest (not exceeding 60 nm), which could potentially result in noticeable fluorescence crosstalk.…”