Electroacupuncture attenuates pulmonary vascular remodeling in a rat model of chronic obstructive pulmonary disease via the VEGF/PI3K/Akt pathway

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is not fully reversible. Pulmonary vascular remodeling is the main pathological feature of COPD. Vascular endothelial growth factor (VEGF), the key regulator of angiogenesis, mediates activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which regulates the proliferation and migration of vascular endothelial cells and plays important roles in pulmonary angiogenesis and remodeling in COPD. Here, the efficacy of electroacupuncture (EA) with respect to regulation of microvascular remodeling induced by VEGF/PI3K/Akt was evaluated in a rat model of COPD. Methods: Rats were randomly assigned to blank, COPD model, EA and sham acupuncture (SA) groups. Rats in the EA group received EA at GV14, BL13 and BL23 three times per week, while those in the SA group, as a control, received shallow and minimal electrostimulation at sites 5–10 mm away from the traditional acupuncture point locations. After 2, 4 and 8 weeks of treatment, the optimal treatment duration was determined according to the results of lung function, lung pathology and inflammatory factor levels. Then, microvessel density, protein levels and mRNA expression of selected VEGF/PI3K/Akt pathway intermediates were determined by immunofluorescence, immunohistochemistry and Western blot analysis, and mRNA qRT-PCR, respectively. Results: EA improved lung function and lung tissue histopathology, with the best effect after 8 weeks of treatment, as noted by reduced density of lung microvessels and expression of angiogenesis-related factors (VEGF and endothelin (ET)-1). EA-treated COPD rats exhibited reduced VEGF, VEGF receptor 2 (VEGFR2), ET-1 mRNA and VEGF, VEGFR2, phosphorylated (p)-VEGFR2, PI3K, Akt, p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR at the protein level in comparison with untreated and SA-treated COPD model rats. Conclusion: EA had beneficial effects on COPD in this animal model including reduced pulmonary vascular remodeling via mechanisms possibly related to the VEGF/PI3K/Akt pathway.

Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study

“…In addition, EA reduces pulmonary vascular remodeling in the COPD model via the PI3K/AKT signaling pathway. In spontaneously hypertensive rats, EA reduces phenotypic transformation of vascular smooth muscle cells via the PI3K/AKT signaling pathway [ 56 , 57 ]. Our results reveal that AKT and PIK3CA expression was upregulated in AMI myocardial tissues and that AKT1 was differentially expressed in MI-CTR and EA-treated MI rats.…”

Ginkgo biloba extract alleviates CCl4-induced acute liver injury by regulating PI3K/AKT signaling pathway

“…PI3K transduction signal can promote the expression of proinflammatory cytokines (such as TNF-α and IL-6) by activating NF-κB downstream of AKT. Further phosphorylation of downstream substrates regulates different functions of cells, such as cell growth, metabolism and apoptosis [ [15] , [16] , [17] , [18] , [19] , [20] ].

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Melatonin and mesenchymal stem cells co-administration alleviates chronic obstructive pulmonary disease via modulation of angiogenesis at the vascular-alveolar unit

“…In addition, Melatonin in the present study showed a significant decrease in VEGF and HIF-1α expression in lung tissue compared to the COPD group. Inhibition of HIF-1α and VEGF, whether at the transcriptional level or HIF-1α degradation, is the main target of Melatonin for inhibition of angiogenesis and oxidative stress especially under hypoxic conditions [ 45 , 68 , 75 , 86 , 88 ]. Other studies showed that depending on the surrounding microenvironment, Melatonin either stimulates or inhibits neovascularization by various mechanisms, producing different biological effects.…”