Uremic toxic substances are essential elements for enhancing carotid artery stenosis after balloon-induced endothelial denudation: worsening role of the adventitial layer

Jiunn Jye Sheu, Chih Chao Yang, Christopher Glenn Wallace, Kuan Hung Chen, Pei Lin Shao, Pei Hsun Sung, Yi Chen Li, Yi Ching Chu, Jun Guo*, Hon Kan Yip*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

This study tested the hypothesis that uremic-toxic substances play a crucial role in enhancing left-common carotid artery (LCCA) stenosis after balloon-denudation of LCCA endothelium (BDLCCAE), and that the adventitial layer plays a complementary role in worsening LCCA stenosis. In vitro results showed the protein expressions of inflammation (IL-1β/TNF-α/IL-6), apoptosis (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and autophagy (beclin/Atg5/LC3B-II to LC3B-I ratio) as well as protein (NOX-1/NOX-2/p22phox/oxidized-protein), total cellular (H2DCFDA) and mitochondrial (Mitosox) levels of oxidative stress were significantly increased in p-Cresol-treated umbilical vein endothelial cells (HUVECs) as compared with control, whereas angiogenesis capacity (i.e., Matrigel-assay for HUVECs) exhibited an opposite pattern to inflammation between the two groups (all P < 0.001). Animals (n = 60) were categorized into group 1 (sham-operated control), group 2 (BDLCCAE), group 3 [BDLCCAE + ESRD patient’s serum (1 cc/injection into deprived CA adventitia)], group 4 [BDLCCAE + ESRD patient’s serum (1 cc/injection from peri-adventitia)], and group 5 [BDLCCAE + ESRD patient’s serum (2 cc/by intravenous injection at days 1/3/7/10/14 after BDLCCADE)] and LCCA was harvested by day-21 after BDLCCAE procedure. Nitric-oxide release from LCCA and the LCCA cross-section area significantly and progressively reduced, whereas intimal and medial layers of LCCA significantly and progressively increased from groups 1 to 5 (all P < 0.001). The cellular expressions of inflammation (CD14+) and DNA-damage biomarker (γ-H2AX+) were significantly and progressively increased, whereas endothelial surface markers (CXCR4/vWF+) were significantly and progressively reduced from groups 1 to 5 (all P < 0.0001). Uremic toxins played an essential role in LCCA remodeling and obstruction. LCCA adventitia facilitated the initiation and propagation of LCCA proliferative obstruction.

原文英語
頁(從 - 到)7144-7159
期刊American Journal of Translational Research
12
發行號11
出版狀態已出版 - 2020

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