The mechanism of RNA oxidation involved in the development of heart failure

• Published in: Free Radical Research Vol. 53; no. 8; pp. 910 - 921
• Main Authors: Liu, Tong, Cai, Jian-Ping, Zhang, Li-Qun, Sun, Ning, Cui, Ju, Wang, Hua, Yang, Jie-Fu
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.08.2019; Informa UK Limited
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - analysis; 8-Hydroxyguanosine; Animals; Chromatography, Liquid; Dahl salt-sensitive rat; Gene Expression Regulation; Guanosine - analogs & derivatives; Guanosine - analysis; heart failure; Heart Failure - genetics; Heart Failure - metabolism; Humans; Male; MAP Kinase Signaling System; Myocardium - metabolism; Oxidation-Reduction; Pyrophosphatases - genetics; Pyrophosphatases - metabolism; Rats; RNA - chemistry; RNA - metabolism; RNA oxidation; Tandem Mass Spectrometry; heart failure; Dahl salt-sensitive rat; 8-Hydroxyguanosine; RNA oxidation
• ISSN: 1071-5762; 1029-2470; 1029-2470
• DOI: 10.1080/10715762.2019.1646424

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.