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Integration of Miniaturized Solid Phase Extraction and LC-MS/MS Detection of 3-Nitrotyrosine in Human Urine for Clinical Applications
Published on: July 14, 2017
3-nitrotyrosine modified proteins in atherosclerosis
1Instituto de Química Biológica, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Insights
Atherosclerosis involves foam cells and oxidative stress. Modified proteins, specifically nitrotyrosine, correlate with cardiovascular disease prevalence, indicating its potential as a predictive biomarker.
Area of Science:
- Cardiovascular research
- Atherosclerosis
- Oxidative stress biology
Background:
- Cardiovascular disease (CVD) is a major cause of global mortality, with atherosclerosis as its primary driver.
- Atherosclerosis is characterized by the accumulation of lipid-laden macrophages (foam cells) and chronic inflammation.
- Oxidative posttranslational modifications, such as protein nitration, occur in atherosclerotic lesions and plasma.
Purpose of the Study:
- To investigate the role of nitrotyrosine modified proteins in atherosclerosis.
- To assess the potential of nitrotyrosine as a biomarker for cardiovascular disease.
Main Methods:
- Analysis of atherosclerotic lesions and plasma from patients.
- Identification and quantification of nitrotyrosine modified proteins.
Main Results:
- Nitrotyrosine modified proteins were detected in atherosclerotic lesions and plasma.
- A significant correlation was observed between plasma protein nitration levels and cardiovascular disease prevalence.
Conclusions:
- Protein nitration, specifically 3-nitrotyrosine, is linked to proatherogenic and prothrombotic properties.
- Nitrotyrosine serves as a valuable biomarker for predicting cardiovascular disease outcomes and guiding therapeutic decisions.
Abstract:
Cardiovascular disease is the leading cause of premature death worldwide, and atherosclerosis is the main contributor. Lipid-laden macrophages, known as foam cells, accumulate in the subendothelial space of the lesion area and contribute to consolidate a chronic inflammatory environment where oxygen and nitrogen derived oxidants are released. Oxidatively modified lipids and proteins are present both in plasma as well as atherosclerotic lesions. A relevant oxidative posttranslational protein modification is the addition of a nitro group to the hydroxyphenyl ring of tyrosine residues, mediated by nitric oxide derived oxidants. Nitrotyrosine modified proteins were found in the lesion and also in plasma from atherosclerotic patients. Despite the fact of the low yield of nitration, immunogenic, proatherogenic, and prothrombotic properties acquired by 3-nitrotyrosine modified proteins are in agreement with epidemiological studies showing a significant correlation between the level of nitration found in plasma proteins and the prevalence of cardiovascular disease, supporting the usefulness of this biomarker to predict the outcome and to take appropriate therapeutic decisions in atherosclerotic disease.
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