scholarly journals Immobilization of Jagged1 Enhances Vascular Smooth Muscle Cells Maturation by Activating the Notch Pathway

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2089
Author(s):  
Kathleen Zohorsky ◽  
Shigang Lin ◽  
Kibret Mequanint
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Notch Pathway ◽  
Muscle Cells ◽  
Serum Starvation ◽  
Specific Response ◽  
Presentation Strategy ◽  
Pulling Forces

In Notch signaling, the Jagged1-Notch3 ligand-receptor pairing is implicated for regulating the phenotype maturity of vascular smooth muscle cells. However, less is known about the role of Jagged1 presentation strategy in this regulation. In this study, we used bead-immobilized Jagged1 to direct phenotype control of primary human coronary artery smooth muscle cells (HCASMC), and to differentiate embryonic multipotent mesenchymal progenitor (10T1/2) cell towards a vascular lineage. This Jagged1 presentation strategy was sufficient to activate the Notch transcription factor HES1 and induce early-stage contractile markers, including smooth muscle α-actin and calponin in HCASMCs. Bead-bound Jagged1 was unable to regulate the late-stage markers myosin heavy chain and smoothelin; however, serum starvation and TGFβ1 were used to achieve a fully contractile smooth muscle cell. When progenitor 10T1/2 cells were used for Notch3 signaling, pre-differentiation with TGFβ1 was required for a robust Jagged1 specific response, suggesting a SMC lineage commitment was necessary to direct SMC differentiation and maturity. The presence of a magnetic tension force to the ligand-receptor complex was evaluated for signaling efficacy. Magnetic pulling forces downregulated HES1 and smooth muscle α-actin in both HCASMCs and progenitor 10T1/2 cells. Taken together, this study demonstrated that (i) bead-bound Jagged1 was sufficient to activate Notch3 and promote SMC differentiation/maturation and (ii) magnetic pulling forces did not activate Notch3, suggesting the bead alone was able to provide necessary clustering or traction forces for Notch activation. Notch is highly context-dependent; therefore, these findings provide insights to improve biomaterial-driven Jagged1 control of SMC behavior.

scholarly journals IGF-I but not insulin inhibits apoptosis at a low concentration in vascular smooth muscle cells

2003 ◽  
Vol 179 (2) ◽  
pp. 267-274 ◽  
Author(s):  
R Jamali ◽  
M Bao ◽  
HJ Arnqvist
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Caspase 3 ◽  
Chromatin Condensation ◽  
Muscle Cells ◽  
Serum Starvation ◽  
Maximal Effect ◽  
Igf I

Apoptosis of vascular smooth muscle cells (VSMCs) is of importance in the development of diabetic angiopathy. Our aim was to evaluate the effect of insulin and IGF-I on apoptosis in VSMCs. Rat aortic VSMCs were used and apoptosis was induced by serum starvation. As apoptotic markers we measured caspase-3 activity, histone-associated DNA fragments by ELISA and nuclear morphology by DAPI (4',6-diamidino-2-phenylindole) staining. Phosphorylation of IGF-I receptors was evaluated by Western blot. Serum starvation had increased caspase-3 activity even after 3 h. The highest activity was found after 3-12 h. IGF-I 10(-9 )M inhibited serum starvation-induced caspase-3 activity with a maximal effect after 12 h. When studied after starvation for 12 h, significant inhibitory effects on caspase-3 were found at IGF-I concentrations of 10(-8)-10(-7) M (P<0.01) and at an insulin concentration of 10(-6 )M (P<0.01). DNA fragmentation was detected by ELISA after 24 h and chromatin condensation and nuclear fragmentation by DAPI staining after 24 and 48 h respectively. IGF-I dose-dependently reduced apoptosis evaluated by ELISA, reaching a maximal effect at 10(-9) M. Insulin reduced apoptosis but the effect was weaker and a higher concentration was needed. IGF-I (10(-8 )M) and insulin at a very high concentration (10(-6) M) phosphorylated IGF-I receptors. Taken together, IGF-I and insulin have antiapoptotic effects on VSMCs but the effect of insulin is only found at high unphysiological concentration.

Serum Starvation and Growth Factor Receptor Expression in Vascular Smooth Muscle Cells

2006 ◽  
Vol 43 (2) ◽  
pp. 157-165 ◽  
Author(s):  
Oliver Zimmermann ◽  
Thomas P. Zwaka ◽  
Nikolaus Marx ◽  
Michael Torzewski ◽  
Andrea Bucher ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Growth Factor Receptor ◽  
Muscle Cells ◽  
Receptor Expression ◽  
Serum Starvation

Isolation of Multiple Types of Plasminogen Activator Inhibitors from Vascular Smooth Muscle Cells

1989 ◽  
Vol 61 (03) ◽  
pp. 517-521 ◽  
Author(s):  
Walter E Laug ◽  
Ruedi Aebersold ◽  
Ambrose Jong ◽  
Willian Rideout ◽  
Barbara L Bergman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Affinity Purification ◽  
Muscle Cells ◽  
Exchange Chromatography ◽  
Natural Resistance ◽  
Protease Nexin ◽  
Pai 1

SummaryLarge arteries have a natural resistance to tumor cell invasion thought to be due to the production of protease inhibitors. Vascular smooth muscle cells (VSMC) representing the major cellular part of arteries were isolated from human aortas and grown in tissue culture. These cells were found to produce large amounts of inhibitors of plasminogen activators (PA). Fractionation of VSMC-conditioned medium by heparin-affigel chromatography separated three immunologically and functionally distinct PA inhibitors (PAI), namely PAI-1, PAI-2 and protease-nexin I. The three inhibitors were characterized by functional assays and immunoblotting. PA inhibitor 2 (PAI-2) had little affinity for heparin, whereas PA inhibitor 1 (PAI-l) bound to heparin and was eluted from the column at NaCl concentrations of 0. 1 to 0.35 M. Protease-nexin I, eluted at NaCl concentrations of 0.5 M and higher. Most of the PAI-1 was present in the latent, inactive form. PAI-1 was further purified by ion exchange chromatography on a Mono-Q column. Partial sequencing of the purified PAI-1 confirmed its nature by matching completely with the sequence deduced from the cDNA nucleotide sequence of endothelial cell PAI-1. Thus, human VSMC produce all three presently known PAI and these can be separated in a single heparin affinity purification step.

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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