Abstract 173: MicroRNA-365 Inhibits the Proliferation of Vascular Smooth Muscle Cells by Targeting Cyclin D1

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of disease progression in atherosclerosis. Cell proliferation is regulated by cell cycle regulatory proteins. MicroRNAs (miRNAs) have been reported to act as important gene regulators and play essential roles in the proliferation and migration of VSMCs in cardiovascular disease. However, the roles and mechanisms of miRNAs in VSMCs and neointimal formation are far from being fully understood. Methods & Results: In this study, cell cycle specific cyclin D1 was found to be a potential target of miR-365 by direct binding. Through an in vitro experiment, we showed that exogenous miR-365 overexpression reduced VSMC proliferation and proliferating cell nuclear antigen (PCNA) expression, while miR-365 was observed to block G1/S transition in platelet-derived growth factor (PDGF)-induced VSMCs. In addition, the proliferation of VSMCs by various stimuli, including PDGF, angiotensin II (Ang II), and serum, led to the downregulation of miR-365 expression levels. The expression of miR-365 was confirmed in balloon injured carotid arteries. Taken together, our results suggest an anti-proliferative role for miR-365 in VSMC proliferation, at least partly via modulating the expression of cyclin D1. Conclusions: Therefore, miR-365 may influence neointimal formation in atherosclerosis patients.

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Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells

Journal of Endocrinology ◽

10.1677/joe.0.1780319 ◽

2003 ◽

Vol 178 (2) ◽

pp. 319-329 ◽

Cited By ~ 38

Author(s):

K Takahashi ◽

M Ohmichi ◽

M Yoshida ◽

K Hisamoto ◽

S Mabuchi ◽

...

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Cyclin D1 ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

G1 Arrest ◽

Cyclin Dependent Kinase ◽

Inhibitory Effects

The proliferation of vascular smooth muscle cells (VSMC) is a crucial pathophysiological process in the development of atherosclerosis. Although estrogen is known to inhibit the proliferation of VSMC, the mechanism responsible for this effect remains to be elucidated. In addition, the effect of raloxifene on VSMC remains unknown. We have shown here that 17beta-estradiol (E(2)) and raloxifene significantly inhibited the platelet-derived growth factor (PDGF)-stimulated proliferation of cultured human VSMC. Flow cytometry demonstrated that PDGF-stimulated S-phase progression of the cell cycle in VSMC was also suppressed by E(2) or raloxifene. We found that PDGF-induced phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by E(2) and raloxifene. These effects were associated with a decrease in cyclin D1 expression, without a change in cyclin-dependent kinase 4 or cyclin-dependent kinase inhibitor, p27(kip1) expression. ICI 182,780 abolished the inhibitory effects of E(2) and raloxifene on PDGF-induced pRb phosphorylation. Next, we examined which estrogen receptor (ER) is necessary for these effects of E(2) and raloxifene. Since VSMC express both ERalpha and ERbeta, A10, a rat aortic smooth muscle cell line that expresses ERbeta but not ERalpha, was used. The dose-dependent stimulation of A10 cell proliferation by PDGF was not inhibited by E(2) or raloxifene in contrast to the results obtained in VSMC. Moreover, E(2) and raloxifene significantly inhibited the PDGF-induced cyclin D1 promoter activity in A10 cells transfected with cDNA for ERalpha but not in the parental cells. These results suggested that E(2) and raloxifene exert an antiproliferative effect in VSMC treated with PDGF, at least in part through inhibition of pRb phosphorylation, and that the inhibitory effects of E(2) and raloxifene may be mainly mediated by ERalpha.

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Cytoglobin overexpression facilitates proliferation and migration of vascular smooth muscle cells

Archives of Biological Sciences ◽

10.2298/abs191024009l ◽

2020 ◽

Vol 72 (2) ◽

pp. 165-172 ◽

Cited By ~ 1

Author(s):

Lei Li ◽

Yilin Xie ◽

Shen Li ◽

Juanjuan Tan ◽

Yingchun Qin ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Feedback Regulation ◽

Muscle Cells ◽

Nuclear Antigen ◽

Matrix Remodeling ◽

Negative Feedback Regulation ◽

Vsmc Proliferation

Cytoglobin, a recently discovered globin, is expressed in vascular smooth muscle cells (VSMCs). Loss of cytoglobin provides a protective effect on vascular reconstruction but the effect of its overexpression is unclear. The aim of the study was to investigate the effect of cytoglobin overexpression on the migration and proliferation of VSMCs and possible mechanisms. We detected the expression of cytoglobin in hypertensive and normotensive rat aortas, with negative feedback regulation between cytoglobin and hypertension observed. The expression of cytoglobin was significantly decreased in hypertensive rats compared to normotensive rats, but VSMCs overexpressing cytoglobin displayed increased cell migration and proliferation, which led to a phenotypic switch. The increased expression of matrix metalloproteinase 9 and collagen Ia suggests a role for cytoglobin in extracellular matrix remodeling. Increased expression of proliferating cell nuclear antigen and decreased expression of p27 implies that cytoglobin is involved in modulating VSMC proliferation. Our findings indicate that cytoglobin may play an important role in vascular wall remodeling.

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Radiation suppresses neointimal hyperplasia through affecting proliferation and apoptosis of vascular smooth muscle cells

The Journal of Vascular Access ◽

10.5301/jva.5000804 ◽

2018 ◽

Vol 19 (2) ◽

pp. 153-161 ◽

Cited By ~ 3

Author(s):

Liqin Yuan ◽

Chang Shu ◽

Xiao Zhou ◽

Jiehua Li ◽

Lunchang Wang ◽

...

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Neointimal Hyperplasia ◽

Muscle Cells ◽

S Phase ◽

Nuclear Antigen ◽

X Ray ◽

Vsmc Proliferation

Purpose: To study the effect of x-ray radiotherapy on vascular smooth muscle cells (VSMCs) and elucidate the mechanisms in preventing neointimal hyperplasia of prosthetic vascular grafts. Materials and methods: In model I, twelve mongrel dogs underwent revascularization with prosthetic grafts and half the dogs underwent irradiation of the grafts at 28 Gy. In model II, human VSMCs (hVSMCs) were maintained and divided into six groups to which external radiation was applied at six different doses: 0 Gy, 2 Gy, 8 Gy, 16 Gy, 24 Gy and 30 Gy. In both models, specimens were harvested and examined by using morphological, immunological, cellular and molecular methods. Results: After irradiation, the neointima thickness was significantly lower in irradiated groups (p≤0.01). The radiotherapy could up-regulate p27kip1, and down-regulate proliferating cell nuclear antigen (PCNA) and S phase kinase associated protein 2 (Skp2). X-ray irradiation inhibits the proliferation of hVSMCs via acting on G1/S phase of cell cycle. The apoptosis of hVSMCs increased significantly with dose and time. The expression of PCNA and Skp2 were decreased after a first increasing trend with dose, but had a significant negative correlation with time. The expression of p27kip1 had a significant positive correlation with dose and time. Conclusions: Postoperative external fractionated irradiation after prosthetic vessel replacement of the abdominal aorta suppressed the development of hyperplasia in the graft neointima in the short term. There was a prominent time- and dose-dependent inhibition of VSMC proliferation by radiation when it was administered.

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Crocetin inhibits cell cycle G1 /S transition through suppressing cyclin D1 and elevating p27kip1 in vascular smooth muscle cells

Phytotherapy Research ◽

10.1002/ptr.3039 ◽

2009 ◽

Vol 24 (7) ◽

pp. 975-981 ◽

Cited By ~ 6

Author(s):

Cheng-Hua Zhou ◽

Min Xiang ◽

Shu-Ying He ◽

Zhi-Yu Qian

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Cyclin D1 ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells

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Mechanism by which avenanthramide-c, a polyphenol of oats, blocks cell cycle progression in vascular smooth muscle cells

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2006.04.020 ◽

2006 ◽

Vol 41 (5) ◽

pp. 702-708 ◽

Cited By ~ 44

Author(s):

Lin Nie ◽

Mitchell Wise ◽

David Peterson ◽

Mohsen Meydani

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Cell Cycle Progression ◽

Muscle Cells ◽

Cycle Progression

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Cell density determines apoptosis and cell cycle arrest in vascular smooth muscle cells in association with p21WAF1/CIP1

Atherosclerosis ◽

10.1016/s0021-9150(00)81087-4 ◽

2000 ◽

Vol 151 (1) ◽

pp. 240

Author(s):

J. Ako ◽

M. Yoshizumi ◽

M. Akishita ◽

S. Kim ◽

M. Hashimoto ◽

...

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Cell Cycle Arrest ◽

Cell Density ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Cycle Arrest

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Molecular cloning of a diverged homeobox gene that is rapidly down-regulated during the G0/G1 transition in vascular smooth muscle cells

Molecular and Cellular Biology ◽

10.1128/mcb.13.6.3722-3733.1993 ◽

1993 ◽

Vol 13 (6) ◽

pp. 3722-3733

Author(s):

D H Gorski ◽

D F LePage ◽

C V Patel ◽

N G Copeland ◽

N A Jenkins ◽

...

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Growth Factor ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Molecular Cloning ◽

Vascular Smooth Muscle Cells ◽

Homeobox Gene ◽

Muscle Cells ◽

Regulatory Function

Adult vascular smooth muscle cells dedifferentiate and reenter the cell cycle in response to growth factor stimulation. Here we describe the molecular cloning from vascular smooth muscle, the structure, and the chromosomal location of a diverged homeobox gene, Gax, whose expression is largely confined to the cardiovascular tissues of the adult. In quiescent adult rat vascular smooth muscle cells, Gax mRNA levels are down-regulated as much as 15-fold within 2 h when these cells are induced to proliferate with platelet-derived growth factor (PDGF) or serum growth factors. This reduction in Gax mRNA is transient, with levels beginning to rise between 8 and 24 h after mitogen stimulation and returning to near normal by 24 to 48 h. The Gax down-regulation is dose dependent and can be correlated with the mitogen's ability to stimulate DNA synthesis. PDGF-AA, a weak mitogen for rat vascular smooth muscle cells, did not affect Gax transcript levels, while PDGF-AB and -BB, potent mitogens for these cells, were nearly as effective as fetal bovine serum. The removal of serum from growing cells induced Gax expression fivefold within 24 h. These data suggest that Gax is likely to have a regulatory function in the G0-to-G1 transition of the cell cycle in vascular smooth muscle cells.

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