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Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
Published on: June 7, 2018
Homocysteine and oxidative stress
A F Perna1, D Ingrosso, N G De Santo
1First Division of Nephrology/Department of Pediatrics, Cardiovascular Research Center, School of Medicine, Second University of Naples, Naples, Italy. alessandra.perna@unina2.it
High homocysteine levels (hyperhomocysteinemia) are linked to cardiovascular disease. Research is ongoing to confirm this causal link and understand homocysteine's toxic mechanisms, like oxidation.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Toxicology
Background:
- Hyperhomocysteinemia is an established independent risk factor for cardiovascular diseases, including ischemic events (stroke, myocardial infarction) and thrombotic events.
- The causal association between hyperhomocysteinemia and cardiovascular disease is suggested by homocystinuria cases and supported by basic science and epidemiological studies.
- Large-scale intervention trials are pending to definitively confirm the causal link.
Purpose of the Study:
- To explore the underlying mechanisms linking hyperhomocysteinemia to cardiovascular disease.
- To elucidate the toxic effects of homocysteine, both cardiovascular and non-cardiovascular.
- To evaluate the evidence for various proposed mechanisms, including oxidation, nitrosylation, acylation, and hypomethylation.
Main Methods:
- Review and analysis of existing basic science and epidemiological evidence.
- Evaluation of proposed mechanisms of homocysteine toxicity.
- Weighing the pros and cons of each postulated mechanism to establish a balance of evidence.
Main Results:
- Hyperhomocysteinemia is a significant risk factor for various cardiovascular and thrombotic events.
- Several mechanisms, including oxidation, nitrosylation, acylation, and hypomethylation, are postulated to explain homocysteine's toxicity.
- The relative importance and evidence supporting each mechanism are currently under investigation.
Conclusions:
- While hyperhomocysteinemia is strongly associated with cardiovascular disease, definitive proof from intervention trials is still needed.
- The precise mechanisms by which homocysteine exerts its toxic effects remain unclear.
- Further research is required to fully understand and potentially mitigate the risks associated with elevated homocysteine levels.
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