Ecklonia cava extracts decrease hypertension-related vascular calcification by modulating PGC-1α and SOD2open access
- Authors
- Byun, Kyung-A; Oh, Seyeon; Yang, Jin Young; Lee, So Young; Son, Kuk Hui; Byun, Kyunghee
- Issue Date
- Sep-2022
- Publisher
- ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
- Keywords
- Peroxisome proliferator-activated receptor-; gamma coactivator-1 alpha; Sirtuin-3; Superoxide dismutase 2; Mitochondrial reactive oxygen species; Ecklonia cava extract
- Citation
- BIOMEDICINE & PHARMACOTHERAPY, v.153
- Journal Title
- BIOMEDICINE & PHARMACOTHERAPY
- Volume
- 153
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/85279
- DOI
- 10.1016/j.biopha.2022.113283
- ISSN
- 0753-3322
- Abstract
- Vascular calcification (VC) is induced by a decrease in sirtuin 3 (SIRT3) and superoxide dismutase (SOD)2 and increases mitochondrial reactive oxygen species (mtROS), eventually leading to mitochondrial dysfunction and phenotype alterations in vascular smooth muscle cells (VSMCs) into osteoblast-like cells in hypertension. Ecklonia cava extract (ECE) is known to increase peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and SOD2. In this study, we evaluated the effect of ECE on decreasing VC by increasing PGC-1 alpha which increased SOD2 activity and decreased mtROS in an in vitro VSMC model of treating serums from Wistar Kyoto (WKY), spontaneous hypertensive rats (SHRs), and ECE-treated SHRs. Furthermore, the decreasing effect of ECE on VC was evaluated with an in vivo SHR model. PGC-1 alpha expression, SIRT3 expression, and SOD2 activity were decreased by the serum from the SHRs and increased by the serum from the ECE-treated SHRs in the VSMCs. PGC-1 alpha silencing eliminated those increases. mtROS generation and mitochondrial DNA (mtDNA) damage increased in the SHRs but decreased with ECE. Mitochondrial fission increased in the SHRs but decreased by ECE. Mitochondrial fusion, mitophagy, and mitochondrial biogenesis were decreased in the SHRs but increased by ECE. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and calcium deposition in the medial layer of the aorta increased in the SHRs but decreased with ECE. Therefore, ECE decreases VC via the upregulation of PGC-1 alpha and SIRT3, which increases SOD2 activity. Activated SOD2 decreases mtDNA damage and mtROS generation, which sequentially decreases NADPH oxidase activity and changes the mitochondrial dynamics, thereby decreasing VC.
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