Sensitively detecting endogenous homocysteine in human serum and cardiomyocytes with a specific fluorescent probe
Huan Li1, Qiwei Wang1, Lili Shi2
1Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, China. tlitao@ustc.edu.cn.
Insights
Elevated homocysteine (Hcy) is a risk factor for acute myocardial infarction (AMI), but this study shows circulating Hcy levels do not directly correlate with cardiomyocyte damage, making it unsuitable for AMI diagnosis.
Area of Science:
- Biochemistry
- Medical Diagnostics
- Fluorescent Probes
Background:
- Elevated homocysteine (Hcy) is a known risk factor for acute myocardial infarction (AMI).
- The diagnostic utility of circulating Hcy levels for AMI remains unclear.
- Biothiols like cysteine (Cys) and glutathione (GSH) can interfere with Hcy detection.
Purpose of the Study:
- To develop a selective fluorescent probe for sensitive Hcy detection in biological samples.
- To investigate the relationship between Hcy levels and AMI.
- To determine if Hcy can serve as a reliable biomarker for AMI diagnosis.
Main Methods:
- Design and synthesis of a tetraazacycle-based fluorescent probe.
- Detection of endogenous Hcy in serum and cardiomyocytes from AMI patients and healthy individuals.
- Statistical analysis of Hcy levels and comparison with other biothiols.
- Assessment of Hcy expression in cardiomyocytes versus other tissue cells.
Main Results:
- The developed probe exhibits high sensitivity and selectivity for Hcy detection over Cys and GSH.
- A significant difference in circulating Hcy levels was observed between AMI patients and healthy participants.
- Endogenous Hcy levels were found to be lower in cardiomyocytes compared to other tissue cells.
- No direct correlation was established between elevated circulating Hcy and cardiomyocyte damage.
Conclusions:
- The fluorescent probe effectively detects Hcy in biofluids.
- Despite being a risk factor, circulating Hcy levels are not a direct indicator of cardiomyocyte damage.
- Circulating Hcy cannot be reliably used as a biomarker for AMI diagnosis.
Abstract:
The elevated level of homocysteine (Hcy) in circulating blood is generally regarded as a risk factor for a variety of diseases including acute myocardial infarction (AMI), but there is no clear answer to whether circulating Hcy can be used for AMI diagnosis. To address it, here we have designed a tetraazacycle-based fluorescent probe for sensitive detection of endogenous Hcy in AMI patients' serum and cardiomyocytes, showing a perfect selectivity over other biothiols (e.g. Cys and GSH). It mainly relies on the formation of a stable six-membered ring structure when this probe responds to Hcy, which is accompanied by a weakening of photoinduced electron transfer (PET) that induces a sharp increase in the fluorescence emission. In this way, Hcy can be probed in biofluids with high sensitivity. We then employed this fluorescent sensor to statistically analyze the levels of Hcy in human circulating blood, indicating a big difference between AMI patients and the healthy participants. To tell whether such a difference is applicable to AMI diagnosis, we further compare the expression levels of Hcy in cardiomyocytes and other tissue cells. It reveals a lower level of endogenous Hcy in cardiomyocytes, implying no direct relationship between the elevated Hcy and cardiomyocyte damage. This observation suggests that Hcy in circulating blood cannot be utilized as a potential biomarker for AMI diagnosis, although it is proven as a risk factor for this disease.
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