Smoothelin

About: Smoothelin is a research topic. Over the lifetime, 264 publications have been published within this topic receiving 14069 citations.

Notch signaling pathway in human vascular smooth muscle cell differentiation

Abstract: Notch receptor-ligand interactions are a highly conserved mechanism, originally described in developmental studies using Drosophilae, that regulate inter-cell communication and dictate, in part, vascular smooth muscle cell (VSMC) fate in response to mechanical stimuli. VSMC differentiation is a crucial developmental process regulating angiogenesis and vasculogenesis, with phenotypic modulation of SMC a key factor in vascular pathology. It has been previously shown that cyclic strain decreases the proliferation of VSMC'S in vitr-u. Tnus, citaraci-erizauon of &e mechani~rils~ "~i ir~l i iirligi ~ b i fk~e~l i iai i~i -~ state of VSMC is of critical importance in determining the cell fate response of these cells to various mechanical stimuli. We investigated the role of Notch 1 and 3 receptor signaling in controlling vascular SMC differentiation in vitro, and established a role for cyclic strain induced changes in Notch in mediating this response. The expression of smouth muscle cell specific a-atin, calponin, myosin and smoothdin was examined by immunocytochemistry, Western blot analysis and quantitative real time PCR in human vascular SMC cultured under static conditions following over-expression of constitutively active Notch 1 and 3 receptors. The effect of equibiaxial cyclic strain (10% 24 h) on the expression of Notch receptors and SMC differentiation was subsequently determined using a Flexercell Tension Plus Unit. Over-expression of constitutively active Notch intracellular receptors (Notch 1 IC and 3 IC) resulted in a significant downregulation of a-actin, calponin, myosin and smoothelin expression, an effect that was significantly attenuated following inhibition of Notch mediated CBF- 1/RBP-Jk dependent signaling by co+xpressia of RPMS-T-I. Cells cultured under conditions of defined equibiaxial cyclic strain (10% strain, 60 cycles/min, 24 h) exhibited a significant reduction in Notch 1 and 3 IC expression, concomitant with a significant increase in smooth muscle cell a-actin, calponin, myosin and smoothelin expression. Moreover, this cyclic strain-induced increase in SMC differentiation marker expression was further enhanced following inhibition of CBF-1/RBP-Jk dependent signaling with RPMS-1. These findings suggest that Notch receptors modulate vascular SMC phenotype in vitro and cyclic strain enhances SMC differentiation in part through inhibition of Notch receptor expression. The Notch signaling pathway may therefore represent a novel mechanism for targeting vascular disorders in which SMC phenotypic diversity occurs in vivo.

Ascending aortas from heart donors and CABG patients are not equivalent as control in aortopathy studies

Abstract: OBJECTIVES A careful selection of reference samples in studies on the pathogenesis of thoracic ascending aorta (TAA) dilation is crucial for reliability, consistency and reproducibility of experimental results. Several studies include control TAA samples from heart donors. Others include samples harvested during coronary artery bypass graft (CABG) procedures or a mix of samples from heart donors and CABG patients. We verified the equivalence/homogeneity of TAA samples from heart donors and CABG patients in terms of basal gene expression and thus their reliability as reference groups in aortopathy studies. DESIGN We analysed by RT-PCR and Western blot the differential expression of smoothelin, α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1), selected as major players in smooth muscle cell and myofibroblast phenotype and remodelling. The mean age and comorbidities of subjects were consistent with data routinely seen in clinical practice. RESULTS Data revealed the loss of smoothelin in samples from CABG patients, together with a significant increase of α-SMA, while TGF-β1 dimer showed a marked increase in CABG patients versus heart donors, accompanied by a decrease of the corresponding mRNA. Differences in gene expression were maintained after adjustment for age. However, TGF-β1 mRNA and CABG patients' age showed a positive correlation (ρ = 0.89, p < .05), while α-SMA mRNA and age showed a negative correlation (ρ = -0.85, p < .05). CONCLUSIONS We revealed the non-equivalence of samples from heart donors and CABG patients, presumably for the presence of microscopic atherosclerotic lesions in CABG patients, suggesting the necessity of a careful selection of control groups in aortopathy studies.

A microRNA‑17‑5p/homeobox B13 axis participates in the phenotypic modulation of vascular smooth muscle cells.

Abstract: Vascular smooth muscle cells (VSMCs) serve a decisive role in intimal hyperplasia, a common pathophysiological process that leads to numerous vascular disorders. The present study aimed to investigate the unknown mechanisms underlying VSMC phenotypic modulation and identified a novel microRNA (miRNA/miR)‑17‑5p/homeobox B13 (HOXB13) axis involved in the phenotypic switching, proliferation and migration of VSMCs. VSMCs were isolated from the thoracic aorta of Sprague‑Dawley rats, cell proliferation was determined by Cell Counting Kit‑8 (CCK‑8) assay, cell migration was examined by Transwell migration assay and gene expression was detected using reverse transcription‑quantitative PCR and western blot analyses. It was firstly found that incubation with platelet‑derived growth factor‑BB (PDGF‑BB) recombinant protein resulted in a significant increase in HOXB13 expression in VSMCs. Using multiple miRNA prediction tools, miR‑17‑5p was identified as a potential regulator for HOXB13, since it had a 7‑base perfect binding site and a 5‑base imperfect binding site with the 3'‑untranslated region of HOXB13 mRNA, and these sequences were highly conserved across species. The regulatory effect of miR‑17‑5p on HOXB13 was validated using luciferase reporter assays. The expression level of miR‑17‑5p was increased in VSMCs under PDGF‑BB stimulation, and was negatively correlated with HOXB13 mRNA and protein expression. Moreover, the miR‑17‑5p mimics significantly inhibited the proliferation and migration of VSMCs, while antagomiR‑17‑5p showed the opposite effects, which could be abolished by HOXB13 knockdown. The miR‑17‑5p/HOXB13 axis also regulated the expression levels of the markers of differentiated VSMCs (α‑smooth muscle actin, transgelin and smoothelin), proliferating cell nuclear antigen and cell migration proteins, including MMP‑2 and ‑9. In conclusion, the present study demonstrated that miR‑17‑5p inhibited the phenotypic modulation VSMCs stimulated by PDGF‑BB by downregulating HOXB13, indicating that these factors may be potential therapeutic targets for intimal hyperplasia.

Device and method for promoting rapid strut coverage and vascular endothelial coverage

Abstract: Myosin heavy chain 11 (MYH11)-siRNA-eluting, calponin 1 (CNN1)-siRNA-eluting, leiomodin 1 (LMOD)-siRNA-eluting, smoothelin (SMTN)-siRNA-eluting, tropomyosin (TPM)-siRNA-eluting, caldesmon 1 (CALD)-siRNA-eluting, actinin (ACTN)-siRNA-eluting, actin alpha (ACTA)-siRNA-eluting, and actin beta (ACTB)-siRNA-eluting medical device capable of selective and significant inhibition of vascular smooth muscle cells (VSMC) in the same or even higher order of magnitude of sirolimus or analogs and paclitaxel or analogs that are cell antiproliferative drugs currently used in drug-eluting stents (DES), whereas said MYH11-siFRNA-eluting, CNN1-siFRNA-eluting, LMOD-siRNA-eluting, SMTN-siRNA-eluting, TPM-siRNA-eluting, CALD-siRNA-eluting, ACTN-siRNA-eluting, ACTA-siRNA-eluting, and ACTB-siRNA-eluting medical devices promote early medical device struts coverage and/or vascular re-endothelialization compared to the current DES that elute cell antiproliferative drugs such as sirolimus or analogs and, paclitaxel or analogs.