The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis

Kim, Jeong‐Han; Jang, Su-Jin; Park, Eunsoo; Oh, Minseok; Park, Sodam; Ko, Jesang

doi:10.1016/j.yjmcc.2014.03.008

Cited by 31 publications

(29 citation statements)

References 30 publications

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“…Our in vitro studies performed in macrophages and endothelial cells, two of the cell types involved in atherosclerosis progression, demonstrated that DMAG impaired inflammatory gene expression in a hyperglycemic environment. These results are in agreement with the recently reported antimigratory effect of HSP90 inhibitor during atherogenesis (41).…”

Section: Discussionsupporting

confidence: 94%

Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice

et al. 2015

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Heat shock proteins (HSPs) are induced by cellular stress and function as molecular chaperones that regulate protein folding. Diabetes impairs the function/expression of many HSPs, including HSP70 and HSP90, key regulators of pathological mechanisms involved in diabetes complications. Therefore, we investigated whether pharmacological HSP90 inhibition ameliorates diabetes-associated renal damage and atheroprogression in a mouse model of combined hyperglycemia and hyperlipidemia (streptozotocin-induced diabetic apolipoprotein E-deficient mouse). Treatment of diabetic mice with 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG, 2 and 4 mg/kg, 10 weeks) improved renal function, as evidenced by dose-dependent decreases in albuminuria, renal lesions (mesangial expansion, leukocyte infiltration, and fibrosis), and expression of proinflammatory and profibrotic genes. Furthermore, DMAG significantly reduced atherosclerotic lesions and induced a more stable plaque phenotype, characterized by lower content of lipids, leukocytes, and inflammatory markers, and increased collagen and smooth muscle cell content. Mechanistically, the renoprotective and antiatherosclerotic effects of DMAG are mediated by the induction of protective HSP70 along with inactivation of nuclear factor-kB (NF-kB) and signal transducers and activators of transcription (STAT) and target gene expression, both in diabetic mice and in cultured cells under hyperglycemic and proinflammatory conditions. In conclusion, HSP90 inhibition by DMAG restrains the progression of renal and vascular damage in experimental diabetes, with potential implications for the prevention of diabetes complications.

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Section: Discussionsupporting

confidence: 94%

Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice

et al. 2015

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“…Functionally, inhibition of HSP90 suppressed migration and proliferation of SMCs in human vascular SMCs, and in mice HSP90 blockage suppressed atherosclerotic plaque formation [38]. It was further deciphered that blockage of HSP90 reduced SMC migration via a downregulation of integrinβ1, and matrix metalloproteinase-2.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…Notably, recent studies including Kim et al identified heat shock protein 90 involvement in atherosclerosis [38]. HSP90 is elevated in arterial plaques of atherosclerosis patients.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…It was further deciphered that blockage of HSP90 reduced SMC migration via a downregulation of integrinβ1, and matrix metalloproteinase-2. In addition, inhibition of HSP90 suppressed SMC proliferation via down-regulation of cyclinD3, proliferating cell nuclear antigen (PCNA) and retinoblastoma protein (pRb) leading to cell cycle arrest [38]. The Kim et al study is not unprecedented, as others have shown that targeted inhibition of elevated HSP90 in SMCs prevents intimal hyperplasia of injured mouse arterial vessels [39].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…gene therapy or pharmacology in preventing neointimal hyperplasia for vascular repair in human atherosclerosis as has been proposed for HSP70 [25] and more recently for HSP90 [38]. 1.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

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Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

2016

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38–AKT–MMP‐2 signaling pathway

Dai

Zhou

et al. 2019

Journal Cellular Physiology

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STRIP2 (FAM40B) was reported to regulate tumor cell migration. Our study aims to discuss the effect of STRIP2 in mouse aortic smooth muscle cell (MOVAS) proliferation and migration processes, which contributes greatly to atherosclerosis formation. In MOVAS cells, STRIP2 depletion suppressed cell proliferation and migration, which were related to a remarkable decrease in matrix metalloproteinases-2 (MMP-2)/MMP-9 expression. Additionally, P38 mitogen-activated protein kinases and Protein kinase B (AKT) are inactivated while extracellular signal-regulated kinase (ERK1/2) and jun N-terminal kinase (JNK) are activated upon STRIP2 silencing. SB203580 (P38 inhibitor) further reduced AKT phosphorylation (p-AKT) while dehydrocorydaline chloride (Dc; P38 activator) reversed this effect. Furthermore, Dc significantly recovered MMP-2 expression in STRIP2-knockdown cells. As expected, overexpressing STRIP2 exhibited a contrary effect. Dc and AKT activator SC79 reversed the inhibition of cell proliferation and migration induced by STRIP2 silencing. Interestingly, STRIP2 depletion increased vascular endothelial growth factor level significantly. Taken together, STRIP2 contributed to cell proliferation and migration through P38-AKT-MMP-2 signaling in MOVAS cells, indicating the importance of STRIP2 in atherosclerosis. K E Y W O R D S cell proliferation and migration, MMP-2, MOVAS, P38, STRIP2

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The role of heat shock protein 90 in migration and proliferation of vascular smooth muscle cells in the development of atherosclerosis

Cited by 31 publications

References 30 publications

Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice

Targeting HSP90 Ameliorates Nephropathy and Atherosclerosis Through Suppression of NF-κB and STAT Signaling Pathways in Diabetic Mice

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells

STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38–AKT–MMP‐2 signaling pathway

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