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miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress.

Mondadori dos Santos A, Metzinger L, Haddad O, M'baya-Moutoula E, Taïbi F, Charnaux N, Massy ZA, Hlawaty H, Metzinger-Le Meuth V - Biomed Res Int (2015)

Bottom Line: Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4.No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs.In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.

ABSTRACT
Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.

No MeSH data available.


Related in: MedlinePlus

miR-126, miR-126, and SDC-4 expression in control and atherosclerotic mice. Twenty-week-old mice aortas were isolated from wild-type (WT) and Apo-E KO mice for miRNA and mRNA studies at the indicated times. CKD mice were subjected to 10 weeks of uremia. (a) miR-126 expression expressed as RQ normalized to U6. (b) SDC-4 expression normalized to GAPDH. Values are expressed as mean ± SD of 3 independent experiments (AU: arbitrary units). Student's t-test, for miR-126: ∗P < 0.05 (WT sham versus Apo-E CKD); for SDC-4: ∗P < 0.05 (WT sham versus WT CKD), ∗P < 0.05 (WT sham versus Apo-E CKD).
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fig5: miR-126, miR-126, and SDC-4 expression in control and atherosclerotic mice. Twenty-week-old mice aortas were isolated from wild-type (WT) and Apo-E KO mice for miRNA and mRNA studies at the indicated times. CKD mice were subjected to 10 weeks of uremia. (a) miR-126 expression expressed as RQ normalized to U6. (b) SDC-4 expression normalized to GAPDH. Values are expressed as mean ± SD of 3 independent experiments (AU: arbitrary units). Student's t-test, for miR-126: ∗P < 0.05 (WT sham versus Apo-E CKD); for SDC-4: ∗P < 0.05 (WT sham versus WT CKD), ∗P < 0.05 (WT sham versus Apo-E CKD).

Mentions: To confirm our findings in an in vivo model, we decided to analyze SDC-4 expression in vessels from a rodent model where miR-126 was shown to be increased [16]. We thus measured concomitantly miR-126 and SDC-4 in aortas from mice models with CKD, atherosclerosis, and vascular calcification [16]. Wild-type (WT) C57/BL6 as well as Apo-E KO mice were submitted to partial nephrectomy to induce CKD. Apo-E KO mice characteristically develop large atheromatous plaques and low-grade vascular calcification and the combination of Apo-E KO/CKD leads to atherosclerosis and aortic calcification [16]. Experiments were performed 10 weeks after induction of uremia, when CKD mice presented severe uremia and Apo-E KO mice presented marked atherosclerosis (data not shown). Under these conditions, miR-126 and SDC-4 expression were also correlated in vivo, as miR-126 expression was increased in the aorta of Apo-E KO/CKD mice (1 versus 3.77 ± 1.29), compared to WT SHAM mice (Figure 5). A significant increase of SDC-4 expression was also observed in WT CKD (1 versus 2.63 ± 1.67) and Apo-E KO/CKD mice (1 versus 3.95 ± 1.3), compared to WT SHAM mice (Figure 5).


miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress.

Mondadori dos Santos A, Metzinger L, Haddad O, M'baya-Moutoula E, Taïbi F, Charnaux N, Massy ZA, Hlawaty H, Metzinger-Le Meuth V - Biomed Res Int (2015)

miR-126, miR-126, and SDC-4 expression in control and atherosclerotic mice. Twenty-week-old mice aortas were isolated from wild-type (WT) and Apo-E KO mice for miRNA and mRNA studies at the indicated times. CKD mice were subjected to 10 weeks of uremia. (a) miR-126 expression expressed as RQ normalized to U6. (b) SDC-4 expression normalized to GAPDH. Values are expressed as mean ± SD of 3 independent experiments (AU: arbitrary units). Student's t-test, for miR-126: ∗P < 0.05 (WT sham versus Apo-E CKD); for SDC-4: ∗P < 0.05 (WT sham versus WT CKD), ∗P < 0.05 (WT sham versus Apo-E CKD).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4499382&req=5

fig5: miR-126, miR-126, and SDC-4 expression in control and atherosclerotic mice. Twenty-week-old mice aortas were isolated from wild-type (WT) and Apo-E KO mice for miRNA and mRNA studies at the indicated times. CKD mice were subjected to 10 weeks of uremia. (a) miR-126 expression expressed as RQ normalized to U6. (b) SDC-4 expression normalized to GAPDH. Values are expressed as mean ± SD of 3 independent experiments (AU: arbitrary units). Student's t-test, for miR-126: ∗P < 0.05 (WT sham versus Apo-E CKD); for SDC-4: ∗P < 0.05 (WT sham versus WT CKD), ∗P < 0.05 (WT sham versus Apo-E CKD).
Mentions: To confirm our findings in an in vivo model, we decided to analyze SDC-4 expression in vessels from a rodent model where miR-126 was shown to be increased [16]. We thus measured concomitantly miR-126 and SDC-4 in aortas from mice models with CKD, atherosclerosis, and vascular calcification [16]. Wild-type (WT) C57/BL6 as well as Apo-E KO mice were submitted to partial nephrectomy to induce CKD. Apo-E KO mice characteristically develop large atheromatous plaques and low-grade vascular calcification and the combination of Apo-E KO/CKD leads to atherosclerosis and aortic calcification [16]. Experiments were performed 10 weeks after induction of uremia, when CKD mice presented severe uremia and Apo-E KO mice presented marked atherosclerosis (data not shown). Under these conditions, miR-126 and SDC-4 expression were also correlated in vivo, as miR-126 expression was increased in the aorta of Apo-E KO/CKD mice (1 versus 3.77 ± 1.29), compared to WT SHAM mice (Figure 5). A significant increase of SDC-4 expression was also observed in WT CKD (1 versus 2.63 ± 1.67) and Apo-E KO/CKD mice (1 versus 3.95 ± 1.3), compared to WT SHAM mice (Figure 5).

Bottom Line: Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4.No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs.In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.

View Article: PubMed Central - PubMed

Affiliation: INSERM U1088, Faculty of Pharmacy and Medicine, University of Picardie Jules Verne, Rue des Louvels, 80037 Amiens, France ; INSERM U1148, LVTS, UFR SMBH, University Paris 13 Sorbonne Paris Cité, 74 rue Marcel Cachin, 93000 Bobigny, France.

ABSTRACT
Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression.

No MeSH data available.


Related in: MedlinePlus