The mechanism of RNA oxidation involved in the development of heart failure |
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Authors: | Tong Liu Jian-Ping Cai Li-Qun Zhang Ning Sun Ju Cui |
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Affiliation: | 1. Graduate School of Peking Union Medical College, Beijing, China;2. Department of Cardiology, Beijing Hospital, National Centre of Gerontology, Beijing, China;3. Peking Union Medical College, Chinese Academy of Medical Science, Beijing, China;4. The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Science, Beijing, China;5. Department of Cardiology, Beijing Hospital, National Centre of Gerontology, Beijing, China |
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Abstract: | Heart failure (HF) has become a global public health problem due to its unclear pathogenesis. Our previous studies have found that RNA oxidation is associated with the occurrence and development of a variety of chronic diseases in the elderly, but whether RNA oxidation is related to the pathogenesis of HF remains unclear. Male Dahl salt-sensitive rats (DSSR) were divided into 8% NaCl groups and 0.3% NaCl groups. The blood pressure of DSSR, HE staining of cardiac tissue, cardiac function index of colour Doppler echocardiography and plasma N-terminal probrain Natriuretic Peptide (NT-ProBNP) were used to evaluate the model making. The levels of 8-hydroxyguanosine (8-oxoGsn) and 8-hydroxydeoxyguanosine (8-oxodGsn) in myocardium and urine of DSSR were determined by high-performance liquid chromatography–mass spectrometry (LC-MS/MS). The expression of ERK-MAPK pathway and MTH1 was detected by Western blot (WB). Rats in the 8% NaCl group developed heart failure symptoms such as increased blood pressure, myocardial hypertrophy, decreased diastolic function, and increased plasma NT-ProBNP. The content of 8-oxoGsn in urine and heart tissue also increased, which was positively correlated with the related indicators of heart failure. This process is also accompanied by the sequential activation of ERK-MAPK pathway molecules and the increase of MTH1. The mechanism of RNA oxidation and inhibition is related to the occurrence and development of HF, which may be involved through ERK-MAPK pathway. |
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Keywords: | 8-Hydroxyguanosine Dahl salt-sensitive rat heart failure RNA oxidation |
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