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Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia

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Title
Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia
Author(s)
Ye Ji Kim; Zinah Hilal Khaleel; Jin, Myeongji; Lee, Jo Woon Yi; Park, Seongchan; Ga, Seongmin; Kim, Nam Hyeong; Sa, Deok Hyang; Kang, Eun Sung; Han, Seul Hee; Lee, Ji Yeun; Ku, Hyo Jung; Kim, Sang-Wook; Kim, Ki Yong; Park, Jeong Euy; Yong Ho Kim; Lee, Bok-Soo
Publication Date
2023-12
Journal
Scientific Reports, v.13, no.1
Publisher
Nature Research
Abstract
High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation. © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/14455
DOI
10.1038/s41598-023-49367-9
ISSN
2045-2322
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > 1. Journal Papers (저널논문)
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