Attenuating Effects of Pyrogallol-Phloroglucinol-6,6-Bieckol on Vascular Smooth Muscle Cell Phenotype Changes to Osteoblastic Cells and Vascular Calcification Induced by High Fat Diet.

Myeongjoo Son,Kyunghee Byun,Chul-Hyun Park,Seyeon Oh,Ji Tae Jang,Kuk Hui Son

doi:10.3390/nu12092777

Myeongjoo Son, Kyunghee Byun + Show 4 more

Open Access

https://doi.org/10.3390/nu12092777

Copy DOI

Abstract

Advanced glycation end products/receptor for AGEs (AGEs/RAGEs) or Toll like receptor 4 (TLR4) induce vascular smooth muscle cell (VSMC) phenotype changes in osteoblast-like cells and vascular calcification. We analyzed the effect of Ecklonia cava extract (ECE) or pyrogallol-phloroglucinol-6,6-bieckol (PPB) on VSMC phenotype changes and vascular calcification prompted by a high-fat diet (HFD). HFD unregulated RAGE, TLR4, transforming growth factor beta (TGFβ), bone morphogenetic protein 2 (BMP2), protein kinase C (PKC), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signals in the aorta of mice. ECE and PPB restored the increase of those signal pathways. AGE- or palmitate-treated VSMC indicated similar changes with the animal. HFD increased osteoblast-like VSMC, which was evaluated by measuring core-binding factor alpha-1 (CBFα-1) and osteocalcin expression and alkaline phosphatase (ALP) activity in the aorta. ECE and PPB reduced vascular calcification, which was analyzed by the calcium deposition ratio, and Alizarin red S stain was increased by HFD. PPB and ECE reduced systolic, diastolic, and mean blood pressure, which increased by HFD. PPB and ECE reduced the phenotype changes of VSMC to osteoblast-like cells and vascular calcification and therefore lowered the blood pressure.

Highlights

Vascular calcification, which is defined as calcified deposits in media or intima, leads to medial calcification of the vessel or atherosclerotic intima calcification [1]
It is well known that the advanced glycation end products (AGEs)/RAGE pathway is involved in vascular calcification by the enhancement of vascular smooth muscle cell (VSMC) phenotype changes to osteoblast-like cells
It seems that high-fat diet (HFD) could increase the expressions of RAGE and Toll like receptor 4 (TLR4) in the adipose tissue and the aorta

Summary

Introduction

Vascular calcification, which is defined as calcified deposits in media or intima, leads to medial calcification of the vessel or atherosclerotic intima calcification [1]. Alkaline phosphatase (ALP) is known to be an early marker of osteoblast activity, while osteopontin and osteocalcin are elevated in the late calcification process [14,15] Those proteins have an important role in the formation and deposition of hydroxyapatite [15]. By AGE binding to RAGE, inflammation-related signaling cascades such as nuclear factor (NF)-κB, extracellular signal-regulated kinase (ERK) 1/2, mitogen-activated protein kinases (p38 MAPK), c-Jun N-terminal kinases (JNK) [16,17], and transforming growth factor β (TGF β) [18] are activated Those signal pathways lead to the upregulation of CBFα-1 and VSMC phenotype changes to osteoblast-like cells [19]

Methods

Results

Conclusion