MiR-200c-3p promotes ox-LDL-induced endothelial to mesenchymal transition in human umbilical vein endothelial cells through SMAD7/YAP pathway

Mao, Yina; Jiang, Ling

doi:10.1186/s12576-021-00815-z

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…In the aortic tissues of ApoE −/− mice and oxLDL-treated HUVECs, miR-200c-3p was highly expressed. miR-200c-3p functions by inhibiting SMAD7 and YAP expression ( 64 ). In addition, LncRNA ZFAS1 was shown to upregulate Notch3 expression via miR-150-5p.…”

Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

108

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Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.

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Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

108

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“…The arterial intimal hyperplasia is closely related to the transition of VSMCs from contractile phenotype to synthetic phenotype 25 and endothelial cell injury. 26 Through immunohistochemistry, we detected the positive expression of α-SMA, the marker of VSMCs with contractile phenotype and found that α-SMA-positive expression was considerably diminished in the HFC group compared with that in the SC group, and the number of α-SMA-positive cells was dramatically increased in the HFC + AM group compared with that in the HFC + AP group (all p < 0.01) (Figure 2(c)). Furthermore, Western blot revealed declined α-SMA protein level and CD31 (endothelial cell marker) and augmented level of OPN (the marker of VSMCs with synthetic phenotype) in the HFC group compared with those in the SC group, suggesting decreased number of VSMCs with contractile phenotype, increased number of VSMCs with synthetic phenotype, and exacerbated endothelial cell injury in the plaques of abdominal aorta of ApoE −/− mice on high-fat diet, while miR-663 overexpression jeopardized the phenotypic transition of VSMCs and attenuated endothelial cell injury (all p < 0.01) (Figure 2(d)).…”

Section: Resultsmentioning

confidence: 92%

Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques

Deng

2022

Vascular

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Objectives Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. microRNAs (miRNAs) are widely distributed in the human body and closely related to the pathological progress of AS. This study probed into the function of miR-663 in AS. Methods The atherosclerotic plaques, cholesterol (CHOL), low-density lipoprotein (LDL), inflammatory factors, and miR-663 expression in ApoE−/− mice on high-fat diet were evaluated. The overexpressing miR-663 adenovirus was injected into ApoE−/− mice, followed by measurement of type III collagen (Col III), matrix metalloproteinase (MMP)-2, α-SMA, osteopontin, and CD31. miR-663 mimic or inhibitor was introduced into vascular smooth muscle cells (VSMCs) stimulated by oxidized LDL (Ox-LDL), and cell proliferation and IL-6 and IL-18 secretion were evaluated. The binding relationship between miR-663 and HMGA2 was verified, followed by the determination of HMGA2 role in VSMC proliferation. Results Atherosclerotic plaques appeared in ApoE−/− mice on high-fat diet, with increased CHOL, LDL, osteopontin, MMP-2 and Col III and decreased miR-663, α-SMA and CD31. miR-663 overexpression downregulated osteopontin, MMP-2 and Col III and upregulated α-SMA and CD31 in ApoE−/− mice on high-fat diet. With Ox-LDL concentration increase, VSMC proliferation was promoted and miR-663 was downregulated. miR-663 overexpression inhibited proliferation of Ox-LDL-stimulated VSMCs and reduced levels of inflammatory factor levels, whereas silencing miR-663 did the opposite. miR-663 targeted HMGA2. HMGA2 overexpression partially reversed the inhibitory effect of miR-663 overexpression on VSMC proliferation. Conclusion miR-663 targeted HMGA2 to inhibit VSMC proliferation and AS development, which may offer insights into AS treatment.

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“…Ox-LDL treatment similarly increased the expression of miR-200c-3p, and co-treatment of HUVECs with ox-LDL with miR-200c-3p potentiated the EndMT phenotype. This effect appeared to be mediated by miR-200c-3p inhibition of the SMAD7/YAP pathway [18].…”

Section: Endothelial To Mesenchymal Transition (Endmt) and Lipids And...mentioning

confidence: 91%

“…The micro-RNA, miR-200c-3p, is overexpressed in atherosclerotic aortic tissue. In the in-vitro experiments using HUVECs, treatment with oxidized LDL (ox-LDL) downregulated endothelial markers CD31 and vWF, while upregulating the mesenchymal markers ɑ-smooth muscle actin and vimentin [18]. Ox-LDL treatment similarly increased the expression of miR-200c-3p, and co-treatment of HUVECs with ox-LDL with miR-200c-3p potentiated the EndMT phenotype.…”

Section: Endothelial To Mesenchymal Transition (Endmt) and Lipids And...mentioning

confidence: 99%

Regulation of cardiovascular calcification by lipids and lipoproteins

Hsu

Tintut

Demer

2022

Current Opinion in Lipidology

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Purpose of reviewLipids and lipoproteins have long been known to contribute to atherosclerosis and cardiovascular calcification. One theme of recent work is the study of lipoprotein (a) [Lp(a)], a lipoprotein particle similar to LDL-cholesterol that carries a long apoprotein tail and most of the circulating oxidized phospholipids.Recent findingsIn-vitro studies show that Lp(a) stimulates osteoblastic differentiation and mineralization of vascular smooth muscle cells, while the association of Lp(a) with coronary artery calcification continues to have varying results, possibly because of the widely varying threshold levels of Lp(a) chosen for association analyses. Another emerging area in the field of cardiovascular calcification is pathological endothelial-to-mesenchymal transition (EndMT), the process whereby endothelial cell transition into multipotent mesenchymal cells, some of which differentiate into osteochondrogenic cells and mineralize. The effects of lipids and lipoproteins on EndMT suggest that they modulate cardiovascular calcification through multiple mechanisms. There are also emerging trends in imaging of calcific vasculopathy, including: intravascular optical coherence tomography for quantifying plaque characteristics, PET with a radiolabeled NaF tracer, with either CT or MRI to detect coronary plaque vulnerability.SummaryRecent work in this field includes studies of Lp(a), EndMT, and new imaging techniques.

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MiR-200c-3p promotes ox-LDL-induced endothelial to mesenchymal transition in human umbilical vein endothelial cells through SMAD7/YAP pathway

Cited by 10 publications

References 28 publications

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Effect of miR-663 on atherosclerosis by regulating the proliferation of vascular smooth muscle cells in lipid plaques

Regulation of cardiovascular calcification by lipids and lipoproteins

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