Reconstituted high-density lipoprotein attenuates atherogenesis partly by regulating HSP27 in hyperlipidemic apoE−/− mice

Lee, Bok-Soo; Kim, Joo Yun; Choi, Jin Yong; Lee, Ji Yeun; Han, Seul Hee; Kim, Ki-Yong; Park, Jeong Euy

doi:10.1016/j.ijcard.2012.09.226

Cited by 3 publications

(3 citation statements)

References 8 publications

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“…However, widely used drugs for drugeluting stents (DES), such as rapamycin or paclitaxel, have been associated with undesirable side effects, including incomplete coverage of stent struts, fibrin deposition, and thrombosis after stenting 2,20,21 . Given the positive results of our previous study, which demonstrated that rHDL produced by Green Cross Corp. can prevent atherosclerotic progression in lesions in hyperlipidemic apoE-/-mice 18 , we sought to investigate whether rHDL could also prevent neointimal hyperplasia using a balloon injury rat model.…”

Section: Discussionmentioning

confidence: 99%

Mechanistic Insights into the Anti-Restenotic Effects of HSP27 and HO1 modulated by Reconstituted HDL on Neointimal Hyperplasia

Lee,

Kim,

Lee

et al. 2023

Preprint

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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. Histological analysis of the injured arteries showed a significant 37% reduction in the intima to media ratio in the group treated with 80 mg/kg rHDL compared to the injury-only group (p<0.05), indicating a specific inhibition of neointimal hyperplasia by rHDL. In vitro analysis confirmed that rHDL significantly suppressed smooth muscle cell (SMC) proliferation while promoting endothelial cell (EC) proliferation. Moreover, treatment with rHDL resulted in reduced infiltration of leukocytes and downregulation of MMP9 expression in the neointimal area. Notably, rHDL administration led to decreased expression of VCAM1 and HIF1α, accompanied by increased expression of heme oxygenase 1 (HO1). Overexpression of HO1 by rHDL effectively inhibited SMC proliferation both in vivo and in vitro. Furthermore, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HO1. Interestingly, HSP27 and HO1 exerted inhibitory effects on the expression of C-C chemokine receptors (CCR2, CCR5, and CCR7), while specifically inhibiting the expression of CX3C motif chemokine receptor 1 (CX3CR1) was observed only with HO1. These findings highlight 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 suppressing leukocytes infiltration and SMC proliferation while promoting EC proliferation.

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Section: Discussionmentioning

confidence: 99%

Mechanistic Insights into the Anti-Restenotic Effects of HSP27 and HO1 modulated by Reconstituted HDL on Neointimal Hyperplasia

Lee,

Kim,

Lee

et al. 2023

Preprint

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show abstract

“…Drug-eluting stents (DES) coated with rapamycin or paclitaxel, are mostly well-known anti-restenotic approaches, however, those have been associated with undesirable side effects, including incomplete coverage of stent struts, fibrin deposition, and thrombosis after stenting 2 , 20 , 21 . Given the positive results of our previous study, which demonstrated that rHDL produced by Green Cross Corp. can prevent atherosclerotic progression in lesions in hyperlipidemic apoE−/− mice 18 , we sought to investigate whether rHDL could also prevent neointimal hyperplasia using a balloon injury rat model.…”

Section: Discussionmentioning

confidence: 99%

“…HDL has been found to inhibit vascular inflammation by inducing HO1 17 . Furthermore, HDL preserves the medial layer and attenuates atherogenesis, partially through upregulation of heat shock protein 27 (HSP27) 18 . Notably, altered expression of HSP27 has been observed in patients with acute coronary syndrome (ACS) and advanced atherosclerotic lesions 19 .…”

Section: Introductionmentioning

confidence: 99%

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

Kim,

Khaleel,

Jin

et al. 2023

Sci Rep

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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.

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Heat shock protein 65 promotes atherosclerosis through impairing the properties of high density lipoprotein

et al. 2014

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Reconstituted high-density lipoprotein attenuates atherogenesis partly by regulating HSP27 in hyperlipidemic apoE−/− mice

Cited by 3 publications

References 8 publications

Mechanistic Insights into the Anti-Restenotic Effects of HSP27 and HO1 modulated by Reconstituted HDL on Neointimal Hyperplasia

Mechanistic Insights into the Anti-Restenotic Effects of HSP27 and HO1 modulated by Reconstituted HDL on Neointimal Hyperplasia

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

Heat shock protein 65 promotes atherosclerosis through impairing the properties of high density lipoprotein

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