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Echinacoside activates Nrf2/PPARγ signaling pathway to modulate mitochondrial fusion-fission balance to ameliorate ox-LDL-induced dysfunction of coronary artery endothelial cells

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Abstract

As a cardiovascular disease, coronary heart disease (CHD) is characterized by poor prognosis and increasing morbidity and mortality rates. Echinacoside (ECH) can protect against multiple cardiovascular diseases due to its antioxidant and anti-inflammatory properties. However, the role of ECH in CHD remains unclear. In ECH-treated human coronary artery endothelial cells (HCAECs), cell viability, NO production, endothelial nitric oxide synthase (eNOS) expression, and angiogenesis ability were detected using cell counting kit-8 (CCK-8) assay, diaminofluorescein-FM diacetate (DAF-FM DA) staining, western blot, and tube formation assay, respectively. The activities of oxidative stress markers were detected using dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay and corresponding assay kits. Cell apoptosis was detected utilizing flow cytometry and caspase3 assay. Western blot was used to detect the expressions of Nrf2/PPARγ signaling pathway- and mitochondrial dynamics-related proteins. Mitochondrial membrane potential and mitochondrial fusion and fission were detected using JC-1 staining and immunofluorescence (IF) assay. In this study, ECH was found to revive the viability, ameliorate the endothelial dysfunction, suppress oxidative stress, and inhibit the apoptosis in ox-LDL-induced HCAECs via activating Nrf2/PPARγ signaling pathway, which were all abolished following the treatment of Nrf2 inhibitor ML385. It was also identified that ECH regulated mitochondrial fusion-fission balance in ox-LDL-induced HCAECs through the activation of Nrf2/PPARγ signaling pathway. In summary, ECH activated Nrf2/PPARγ signaling pathway to regulate mitochondrial fusion-fission balance, thereby improving ox-LDL-induced dysfunction of HCAECs.

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The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, The Ninth People’s Hospital of Chongqing, Chongqing, China

    Xiandi Qiu

  2. Department of Neurology, The Ninth People’s Hospital of Chongqing, No. 69 Jialing Village, Beibei District, Chongqing, 400700, China

    Yuxing Feng

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  1. Xiandi Qiu
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Contributions

Xiandi Qiu and Yuxing Feng conceived the experiments. Xiandi Qiu performed the experiments. Xiandi Qiu analyzed the data. Xiandi Qiu and Yuxing Feng confirmed the authenticity of all the raw data. Both authors have read and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Yuxing Feng.

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Qiu, X., Feng, Y. Echinacoside activates Nrf2/PPARγ signaling pathway to modulate mitochondrial fusion-fission balance to ameliorate ox-LDL-induced dysfunction of coronary artery endothelial cells. Naunyn-Schmiedeberg's Arch Pharmacol 397, 9767–9776 (2024). https://doi.org/10.1007/s00210-024-03233-1

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