Yuhua Shen1, Wen Zhang1, Lijun Lee2, Mianming Hong2, Minfei Lee2, Guohui Chou2, Li Yu2, Yuqing Sui2, Baihua Chou3. 1. Department of Cardiology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 518106, Guangdong, China. 2. Nanhai Hospital, Southern Medical University Carvascular Medicine, Foshan 528244, Guangdong, China. 3. Nanhai Hospital, Southern Medical University Carvascular Medicine, Foshan 528244, Guangdong, China. Electronic address: choubaihua777@163.com.
Abstract
OBJECTIVE: Little is known regarding the functional role of microRNA-195-5p (miR-195-5p) in heart failure (HF). Hence, the aim of the present study was to investigate the effect of miR-195-5p on cardiac function in mice with HF and its mechanism through the regulation of Chemokine receptor type 4 (CXCR4) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. METHODS: The mice model of HF was established by transverse aortic constriction, the successfully modeled mice were injected with anti-miR-195-5p and OE-CXCR4. The expression of miR-195-5p, CXCR4, JAK2 and STAT1 in the myocardial tissues of each group were detected. The target relationship between miR-195-5p and CXCR4 was verified. The indices of cardiac ultrasound, hemodynamics, oxidative stress, inflammatory factor, myocardial enzyme and cardiac function were detected. RESULTS: MiR-195-5p, JAK2 and STAT1 expression were raised and CXCR4 expression was degraded in myocardial tissues of HF mice and CXCR4 was the target gene of miR-195-5p. Down-regulated miR-195-5p and up-regulated CXCR4 ameliorated cardiac function, abated inflammatory factors contents, oxidative stress reaction and myocardial enzyme indices in HF mice. Down-regulated miR-195-5p and up-regulated CXCR4 suppressed apoptosis of cardiomyocytes in HF mice. CONCLUSION: Depleting miR-195-5p and up-regulating CXCR4 alleviates cardiac function injury in mice with HF via inhibition of JAK/STAT signaling pathway activation. MiR-195-5p might be a potential candidate marker and therapeutic target for HF.
OBJECTIVE: Little is known regarding the functional role of microRNA-195-5p (miR-195-5p) in heart failure (HF). Hence, the aim of the present study was to investigate the effect of miR-195-5p on cardiac function in mice with HF and its mechanism through the regulation of Chemokine receptor type 4 (CXCR4) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. METHODS: The mice model of HF was established by transverse aortic constriction, the successfully modeled mice were injected with anti-miR-195-5p and OE-CXCR4. The expression of miR-195-5p, CXCR4, JAK2 and STAT1 in the myocardial tissues of each group were detected. The target relationship between miR-195-5p and CXCR4 was verified. The indices of cardiac ultrasound, hemodynamics, oxidative stress, inflammatory factor, myocardial enzyme and cardiac function were detected. RESULTS:MiR-195-5p, JAK2 and STAT1 expression were raised and CXCR4 expression was degraded in myocardial tissues of HFmice and CXCR4 was the target gene of miR-195-5p. Down-regulated miR-195-5p and up-regulated CXCR4 ameliorated cardiac function, abated inflammatory factors contents, oxidative stress reaction and myocardial enzyme indices in HFmice. Down-regulated miR-195-5p and up-regulated CXCR4 suppressed apoptosis of cardiomyocytes in HFmice. CONCLUSION: Depleting miR-195-5p and up-regulating CXCR4 alleviates cardiac function injury in mice with HF via inhibition of JAK/STAT signaling pathway activation. MiR-195-5p might be a potential candidate marker and therapeutic target for HF.