Acupuncture Promotes Angiogenesis after Myocardial Ischemia through H3K9 Acetylation Regulation at VEGF Gene

Abstract

BackgroundAcupuncture exerts cardioprotective effects on several types of cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and its modification through histone acetylation has been considered a target in treating myocardial ischemia. This study aims to exam whether modulation of angiogenesis through H3K9 acetylation regulation at VEGF gene is one possible cardioprotective mechanism of acupuncture.ResultsWe generated rat MI models by ligating the left anterior descending coronary artery and applied electroacupuncture (EA) treatment at the Neiguan (PC6) acupoint. Our results showed that acupuncture reversed the S-T segment change, reduced Q-wave area, decreased CK, CK-MB, LDH levels, mitigated myocardial remodeling, and promoted microvessel formation in the MI heart. RNA-seq analysis showed that VEGF-induced angiogenesis signaling was involved in the modulation of EA. Western blot results verified that the protein expressions of VEGF, Ras, phospho-p44/42 MAPK, phospho-p38 MAPK, phospho-SAPK/JNK and Akt, were all elevated significantly by EA treatment in the MI heart. Furthermore, increased H3K9 acetylation was also observed according with the VEGF. ChIP assay confirmed that EA treatment could notably stimulate the recruitment of H3K9ace at the VEGF promoter.ConclusionsOur study demonstrates for the first time that acupuncture can effectively up-regulate VEGF expression through H3K9 acetylation modification directly at the VEGF promoter and hence activate VEGF-induced angiogenesis in rat MI models. We employed high throughput sequencing in this study and, for the first time, generated genome-wide gene expression profiles both in the rat MI model and in acupuncture treatment.

Combined treatment with sinomenine and acupuncture on collagen‑induced arthritis through the NF‑κB and MAPK signaling pathway

“…In particular, MMP2, MMP3 and MMP13 are the primary proteinases responsible for the acceleration of ECM degradation in RA (30). Therefore, repression of MMP2 and MMP9 expression may be a potential therapeutic strategy for RA in the future (30). Results of the present study indicated that CC treatment significantly suppressed p-p38 protein expression, and MMP2/MMP9 levels in collagen-induced arthritic rabbits when compared with acupuncture or sinomenine treatment alone.…”

“…Furthermore, MMPs are essential in RA disease progression as these molecules degrade the vast majority of cartilage ECM within the cartilago articularis (29). In particular, MMP2, MMP3 and MMP13 are the primary proteinases responsible for the acceleration of ECM degradation in RA (30). Therefore, repression of MMP2 and MMP9 expression may be a potential therapeutic strategy for RA in the future (30).…”

“…Results of the present study indicated that CC treatment significantly suppressed p-p38 protein expression, and MMP2/MMP9 levels in collagen-induced arthritic rabbits when compared with acupuncture or sinomenine treatment alone. Fu et al (30) demonstrated that acupuncture promotes angiogenesis following myocardial ischemia through p38-MAPK expression.…”

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

“…EA is generally recommended as a treatment for ischemic heart injury, including AMI [22,23]. IMA, HCY and LP-PLA2 are markers for AMI [24][25][26].…”

Electroacupuncture Ameliorates Acute Myocardial Ischemia: A Potential Role of the Locus Coeruleus

“…Acupuncture, which derives from ancient China, is an important component of TCM. is alternative therapy can prevent and treat many diseases, including AMI [7,8]. Clinical studies [9,10] have indicated that acupuncture can improve cardiac function and promote recovery from myocardial ischemia.…”