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Volume 18
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10.3390/md18080393
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Article

Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5

by
Seyeon Oh
1,†,
Myeongjoo Son
1,2,†,
Chul-Hyun Park
3,
Ji Tae Jang
4,
Kuk Hui Son
3,* and
Kyunghee Byun
1,2,*
1
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea
2
Department of Anatomy & Cell Biology, Graduate School of Medicine, Gachon University, Incheon 21936, Korea
3
Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea
4
Aqua Green Technology Co., Ltd., Smart Bldg., Jeju Science Park, Cheomdan-ro, Jeju 63243, Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Mar. Drugs 2020, 18(8), 393; https://doi.org/10.3390/md18080393
Submission received: 29 June 2020 / Revised: 21 July 2020 / Accepted: 21 July 2020 / Published: 27 July 2020
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Abstract

Hyperlipidemia induces vascular smooth muscle cell (VSMC) proliferation and phenotype switching from contractile to synthetic. This process is involved in arterial remodeling via the chemokine ligand 5 (CCL5)/chemokine receptor 5 (CCR5) pathway. Arterial remodeling is related to atherosclerosis or intimal hyperplasia. The purpose of this study was to evaluate whether pyrogallol-phloroglucinol-6,6-bieckol (PPB) from E. cava reduces VSMC proliferation and phenotype switching via the CCL5/CCR5 pathway. The CCL5/CCR5 expression, VSMC proliferation and phenotypic alterations were evaluated using a cell model of VSMC exposed in hyperlipidemia, and an animal model of mice fed a high-fat-diet (HFD). The expression of CCL5/CCR5 increased in both the cell and animal models of hyperlipidemia. Treatment with PPB decreased CCL5/CCR5 expression in both models. The expression of contractile markers of VSMCs, including alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), and smooth muscle protein 22 alpha (SM22α), were decreased by hyperlipidemia and restored after treatment with PPB. The silencing of CCR5 attenuated the effects of PPB treatment. VSMC proliferation and the intima-media thickness of the aortas, increased with HFD and decreased after treatment with PPB. The VSMC proliferation ratio and messenger ribonucleic acid (mRNA) expression of cell cycle regulatory factors increased in the in vitro model and were restored after treatment with PPB. PPB treatment reduced VSMC proliferation and phenotype switching induced by hyperlipidemia through inhibition of the CCL5/CCR5 pathway.
Keywords: Ecklonia cava; pyrogallol-phloroglucinol-6,6′-bieckol; vascular smooth muscle cell proliferation; vascular smooth muscle cell phenotype switching; chemokine receptor 5 Ecklonia cava; pyrogallol-phloroglucinol-6,6′-bieckol; vascular smooth muscle cell proliferation; vascular smooth muscle cell phenotype switching; chemokine receptor 5

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MDPI and ACS Style

Oh, S.; Son, M.; Park, C.-H.; Jang, J.T.; Son, K.H.; Byun, K. Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5. Mar. Drugs 2020, 18, 393. https://doi.org/10.3390/md18080393

AMA Style

Oh S, Son M, Park C-H, Jang JT, Son KH, Byun K. Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5. Marine Drugs. 2020; 18(8):393. https://doi.org/10.3390/md18080393

Chicago/Turabian Style

Oh, Seyeon, Myeongjoo Son, Chul-Hyun Park, Ji Tae Jang, Kuk Hui Son, and Kyunghee Byun. 2020. "Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5" Marine Drugs 18, no. 8: 393. https://doi.org/10.3390/md18080393

APA Style

Oh, S., Son, M., Park, C.-H., Jang, J. T., Son, K. H., & Byun, K. (2020). Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5. Marine Drugs, 18(8), 393. https://doi.org/10.3390/md18080393

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