Evidence Details for Akt1
PMID Title Journal Year Abstract
24722278 Acupuncture promotes angiogenesis after myocardial ischemia through H3K9 acetylation regulation at VEGF gene. PLoS One. 2014 Apr 10;9(4):e94604. doi: 10.1371/journal.pone.0094604. eCollection 2014. 2014 BACKGROUND: Acupuncture 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. RESULTS: We 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. CONCLUSIONS: Our 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."

Evidence Sentence: 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.
Evidence Sentence: Pathway analysis indicated that these co-regulated genes were mainly involved in the calcium signaling pathway, cardiomyopathy related pathways, and cancer related pathways (Fig 4C and 4D), such as VEGF, an angiogenic factor, and VEGF-activated signaling component, including Ras, Akt and MAPK family members, decreased in the MI group, but significantly increased in the EA group (Table 1).
Evidence Sentence: Western blot results showed that VEGF protein expression was decreased obviously, accompanying with the decrease of Ras, phospho-p44/42 MAPK, phospho-p38 MAPK, phospho-SAPK/JNK and Akt proteins in the MI group.
Evidence Sentence: Surprisingly, in CEA group, the expressions of VEGF, phospho-p44/42 MAPK and phospho-p38 MAPK were also decreased, meanwhile phospho-SAPK/JNK and Akt expressions were significantly increased.