Soluble epoxide hydrolase and ischemic cardiomyopathy
Ting-Ting Zhao1, Binaya Wasti, Dan-Yan Xu
1Department of Cardiovascular Internal Medicine, Second Xiangya Hospital, Central South University Changsha, 410011, PR China.
Insights
Lowered epoxyeicosatrienoic acids (EETs) are linked to cardiovascular disease. Soluble epoxide hydrolase inhibitors (sEHIs) show promise in treating ischemic cardiomyopathy by increasing EETs levels.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Pharmacology
Background:
- Cardiovascular disease development is associated with reduced epoxyeicosatrienoic acids (EETs).
- Ischemic cardiomyopathy, characterized by atherosclerotic lesions, leads to myocardial dysfunction and heart failure.
- The EPHX2 gene encodes soluble epoxide hydrolase (sEH), which metabolizes EETs and has known polymorphisms linked to cardiovascular disease.
Purpose of the Study:
- To investigate the role of sEH in ischemic cardiomyopathy.
- To explore the therapeutic potential of sEH inhibitors (sEHIs) in cardiovascular diseases.
Main Methods:
- Review of existing research on sEH, EETs, and their role in cardiovascular pathology.
- Analysis of the mechanisms by which sEHIs modulate EETs levels and cardiovascular function.
Main Results:
- sEH activity and polymorphisms are implicated in cardiovascular diseases.
- sEHIs effectively increase EETs concentrations by inhibiting EETs hydration.
- sEHIs demonstrate potential in preventing atherosclerosis, improving coronary artery function, and mitigating ischemia-reperfusion injury.
Conclusions:
- Soluble epoxide hydrolase (sEH) is an etiological factor in cardiovascular diseases, particularly in the progression of myocardial ischemia.
- Soluble epoxide hydrolase inhibitors (sEHIs) represent a novel therapeutic strategy for the prevention and treatment of ischemic cardiomyopathy.
Background:
The development of cardiovascular disease has been linked to lowered levels of epoxyeicosatrienoic acids (EETs) in the cardiovascular system. Ischemic cardiomyopathy is caused by atherosclerotic lesions in multi-coronary arteries especially diffusive lesions, which can lead to severe myocardial dysfunction, heart enlargement, heart failure, or arrhythmia, and so on. The EETs are metabolized by the soluble epoxide hydrolase (sEH) encoded by the EPHX2 gene that has several known polymorphisms.
Content:
The EPHX2 gene polymorphism is associated with sEH catalytic activity and various cardiovascular diseases. sEH is distributed in a variety of organs and tissues and regulated by multiple factors. Research in the area has led to the presence of multiple powerful soluble epoxide hydrolase inhibitors (sEHIs), whose molecular structure and function has been optimized gradually. sEHIs increase EETs' concentration by inhibiting hydration of EETs into their corresponding vicinal diols. EETs are important signaling molecules and known as endothelium-derived hyperpolarizing factors (EDHF). sEHIs have been developed for their ability to prevent atherosclerosis, dilate the coronary artery, promote angiogenesis, ameliorate postischemic recovery of heart contractile function, decrease ischemia/reperfusion injury, modulate postischemic arrhythmia, and prevent heart failure.
Summary:
sEH is one of the etiological factors of cardiovascular diseases, and plays an important role in the progression of myocardium ischemia. This indicates that sEHIs provide a new method for the prevention and treatment of ischemic cardiomyopathy.
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