Endogenous VEGF-A is responsible for mitogenic effects of MCP-1 on vascular smooth muscle cells

2004 ◽  
Vol 286 (5) ◽  
pp. H1978-H1984 ◽  
Author(s):  
Astrid Parenti ◽  
Lydia Bellik ◽  
Laura Brogelli ◽  
Sandra Filippi ◽  
Fabrizio Ledda
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vsmc Proliferation ◽  
Low Concentrations ◽  
Receptor Upregulation ◽  
And Migration ◽  
Proliferation And Migration

Vessel wall remodeling is a complex phenomenon in which the loss of differentiation of vascular smooth muscle cells (VSMCs) occurs. We investigated the role of rat macrophage chemoattractant protein (MCP)-1 on rat VSMC proliferation and migration to identify the mechanism(s) involved in this kind of activity. Exposure to very low concentrations (1–100 pg/ml) of rat MCP-1 induced a significant proliferation of cultured rat VSMCs assessed as cell duplication by the counting of total cells after exposure to test substances. MCP-1 stimulated VSMC proliferation and migration in a two-dimensional lateral sheet migration of adherent cells in culture. Endogenous vascular endothelial growth factor-A (VEGF-A) was responsible for the mitogenic activity of MCP-1, because neutralizing anti-VEGF-A antibody inhibited cell proliferation in response to MCP-1. On the contrary, neutralizing anti-fibroblast growth factor-2 and anti-platelet-derived growth factor-bb antibodies did not affect VSMC proliferation induced by MCP-1. RT-PCR and Western blot analyses showed an increased expression of either mRNA or VEGF-A protein after MCP-1 activation (10–100 pg/ml), whereas no fms-like tyrosine kinase (Flt)-1 receptor upregulation was observed. Because we have previously demonstrated that hypoxia (3% O2) can enhance VSMC proliferation induced by VEGF-A through Flt-1 receptor upregulation, the effects of hypoxia on the response of VSMCs to MCP-1 were investigated. Severe hypoxia (3% O2) potentiated the growth-promoting effect of MCP-1, which was able to significantly induce cell proliferation even at a concentration as low as 0.1 pg/ml. These findings demonstrate that low concentrations of rat MCP-1 can directly promote rat VSMC proliferation and migration through the autocrine production of VEGF-A.

scholarly journals MiR-9 promotes the phenotypic switch of vascular smooth muscle cells by targeting KLF5

2019 ◽  
Author(s):  
XIAOCHUN LU ◽  
SHITANG MA ◽  
BO ZHOU ◽  
TIELING LI
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Phenotypic Switch ◽  
Vsmc Proliferation ◽  
Qrt Pcr ◽  
And Migration ◽  
Proliferation And Migration

Background: Diabetic vascular smooth muscle cells (VSMCs) are characterized by increased proliferation and migration. Small non-coding microRNAs (miRNAs) have been considered critical modulators of VSMC phenotypic switch after an environmental stimulus. However, microRNA in high glucose-induced pro-inflammation and its atherogenic effect is still ambiguous. Methods: qRT-PCR was used to examine the expression of miR-9 in VSMCs. The downstream signaling protein relative to miR-9 regulation, Krüppel-like factor 5, and some marker genes of contractile VSMCs, were analyzed by western blotting and qRT-PCR. Luciferase reporter assay was used to detect the expression of KLF5, which is regulated by miR-9. To examine the function of a miR-9 inhibitor in VSMC proliferation and migration, VSMC proliferation and migration assays were performed. Results: Reduced transcriptional levels of miR-9 and expression of specific genes of contractile VSMCs were observed in the SMC cell line C-12511 treated with high glucose and SMCs, which were isolated from db/db mice. Moreover, the activity of KLF5 3′-UTR was dramatically reduced by a miR-9 mimic, and increased by a miR-9 inhibitor. The proliferation and migration of SMCs was reduced by the miR-9 mimic. Conclusion: miR-9 inhibits the proliferation and migration of SMC by targeting KLF5 in db/db mice. Keywords: miR-9; Smooth muscle cells; Proliferation; Migration; KLF5

scholarly journals Knockdown of long non-coding RNA OIP5-AS1 suppresses cell proliferation and migration in ox-LDL-induced human vascular smooth muscle cells (hVMSCs) through targeting miR-152-3p/PAPPA axis

RSC Advances ◽  
2019 ◽  
Vol 9 (56) ◽  
pp. 32499-32509 ◽  
Author(s):  
Xiangya Yang ◽  
Zhongrui Li ◽  
Lei Zhang ◽  
Xiaoshan Wu ◽  
Qixin Kang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Cell Proliferation And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Proliferation And Migration

Knockdown of OIP5-AS1 suppressed ox-LDL-treated hVMSCs proliferation and migration; overexpression of miR-152 played the similar role of OIP5-AS1 knockdown; OIP5-AS1 functioned as ceRNA to regulate PAPPA expression through sponging miR-152.

scholarly journals LINC01123 Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells and Alleviates Carotid Atherosclerosis by Modulating miR-1277-5p/KLF5

2020 ◽  
Author(s):  
Guohu Weng ◽  
Minhua Gu ◽  
Yifan Zhang ◽  
Guangfeng Zhao ◽  
Yong Gu
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Carotid Atherosclerosis ◽  
Muscle Cells ◽  
And Migration ◽  
Klf5 Expression ◽  
Proliferation And Migration

Abstract Background: The pathophysiological mechanism of carotid atherosclerosis (CAS) involves endothelial cell dysfunction, vascular smooth muscle cells (VSMCs) and macrophage activation, which ultimately leads to fibrosis of the vessel wall. lncRNA works weightily in the formation of CAS, but the function and mechanism of lncRNA LINC01123 in CAS are still equivocal.Methods: We collected blood samples from 35 CAS patients as well as 33 healthy volunteers. VSMCs treated with oxidized low-density lipoprotein (ox-LDL) were utilized as the CAS cell model. We applied qRT-PCR for detecting LINC01123, miR-1277-5p and KLF5 mRNA expression, CCK-8 method and BrdU test for determining cell proliferation, Transwell test for measuring cell migration, as well as Western blot for assaying KLF5 protein expression. Dual-luciferase reporter experiment was adopted for assessing the interaction between LINC01123 and miR-1277-5p, as well as KLF5 and miR-1277-5p.Results: LINC01123 and KLF5 expression was dramatically up-regulated, while miR-1277-5p expression was down-regulated in CAS patients and ox-LDL-induced CAS cell models. Overexpressed LINC01123 notedly promoted VSMC migration and proliferation. LINC01123 knockdown repressed cell proliferation and migration. Also, LINC01123 targeted miR-1277-5p and down-regulated its expression, while miR-1277-5p could negatively regulate KLF5 expression.Conclusion: LINC01123 is highly expressed in CAS patients and is capable of being utilized as a latent target for treating CAS.

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