Abstract
BackgroundThe pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome.MethodsAdult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment.ResultsThe results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI.ConclusionsOur findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.
Highlights
The pathological process of myocardial ischemia (MI) is very complicated
Acupuncture treatment at the PC6 acupoint effectively protected the myocardium from MI injury To investigate the effects of acupuncture at PC6 acupoint on myocardial injury, we first assessed the cardiac function and infarct area
Echocardiography results indicated that both EF and FS significantly decreased after MI compared with the control group
Summary
The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. Since the pathological process and mechanism of MI injury is complicated, which involved in cardiac fibrosis [29], inflammation [42], angiogenesis [28], apoptosis [2], Gene regulation is a fundamental process in developing and disease progression, and transcriptome research a necessary tool for understanding the gene. The effect of acupuncture on genome-wide gene expressions in myocardial ischemia models has not been reported. Most researches on the transcriptome of acupuncture effect on heart diseases are relatively limited and primarily focuses on differential genes. Research proved that alternative splicing in titin (TTN) could modify sarcomeric stiffness to influence cardiac function [34]. The role of alternative splicing in myocardial ischemia has not been well understood. Some new genes which structure and function have not been reported can be identified by full-length transcriptome, these new genes may be the critical targets for acupuncture
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