The Cytoskeletal Network Regulates Expression of the Profibrotic Genes PAI-1 and CTGF in Vascular Smooth Muscle Cells

2018 ◽  
pp. 79-94 ◽  
Author(s):  
Rohan Samarakoon ◽  
Paul J. Higgins
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cytoskeletal Network ◽  
Pai 1

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.

LRP and αvβ3 mediate tPA activation of smooth muscle cells

2006 ◽  
Vol 291 (3) ◽  
pp. H1351-H1359 ◽  
Author(s):  
Sa'ed Akkawi ◽  
Taher Nassar ◽  
Mark Tarshis ◽  
Douglas B. Cines ◽  
Abd Al-Roof Higazi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Plasminogen Activator ◽  
Vascular Smooth Muscle Cells ◽  
Density Lipoprotein ◽  
Plasminogen Activator Inhibitor ◽  
Muscle Cells ◽  
Tissue Type ◽  
Pai 1

Tissue-type plasminogen activator (tPA) regulates vascular contractility through the low-density lipoprotein-related receptor (LRP), and this effect is inhibited by plasminogen activator inhibitor type 1 (PAI-1). We now report that tPA-mediated vasocontraction also requires the integrin αvβ3. tPA-induced contraction of rat aortic rings is inhibited by the Arg-Gly-Asp (RGD) peptide and by monoclonal anti-αvβ3 antibody. tPA induces the formation of a complex between LRP and αvβ3 in vascular smooth muscle cells. The three proteins are internalized within 10 min, causing the cells to become refractory to the readdition of tPA. LRP and αvβ3 return to the cell surface by 90 min, restoring cell responsiveness to tPA. PAI-1 and the PAI-1-derived hexapeptide EEIIMD abolish the vasocontractile activity of tPA and inhibit the tPA-mediated interaction between LRP and αvβ3. tPA induces calcium mobilization from intracellular stores in vascular smooth muscle cells, and this effect is inhibited by PAI-1, RGD, and antibodies to both LRP and αvβ3. These data indicate that tPA-mediated vasocontraction involves the coordinated interaction of LRP with αvβ3. Delineating the mechanism underlying these interactions and the nature of the signals transduced may provide new tools to regulate vascular tone and other consequences of tPA-mediated signaling.

scholarly journals Receptor-dependent prorenin activation and induction of PAI-1 expression in vascular smooth muscle cells

2008 ◽  
Vol 295 (4) ◽  
pp. E810-E819 ◽  
Author(s):  
Jiandong Zhang ◽  
Nancy A. Noble ◽  
Wayne A. Border ◽  
Rick T. Owens ◽  
Yufeng Huang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Tissue ◽  
Microvascular Complications ◽  
Muscle Cells ◽  
Diabetic Patients ◽  
Ang Ii ◽  
Pai 1

Although elevated plasma prorenin levels are commonly found in diabetic patients and correlate with microvascular complications, the pathological role of these increases, if any, remains unclear. Prorenin/renin binding to the prorenin/renin receptor [(p)RR] enhances the efficiency of angiotensinogen cleavage by renin and unmasks prorenin catalytic activity. We asked whether plasma prorenin could be activated in local vascular tissue through receptor binding. Immunohistochemical staining showing localization of the (p)RR in the aorta to vascular smooth muscle cells (VSMCs). After cultured rat VSMCs were incubated with 10−7 M inactive prorenin, cultured supernatant acquired the ability to generate ANG I from angiotensinogen, indicating that prorenin had been activated. Activated prorenin facilitated angiotensin generation in cultured VSMCs when exogenous angiotensinogen was added. Small interfering RNA (siRNA) against the (p)RR blocked this activation and subsequent angiotensin generation. Prorenin alone induced dose- and time-dependent increases in mRNA and protein for the profibrotic molecule plasminogen activator inhibitor (PAI)-1, effects that were blocked by siRNA, but not by the ANG II receptor antagonist saralasin. When inactive prorenin and angiotensinogen were incubated with cells, PAI-1 mRNA increased a striking 54-fold, 8-fold higher than the increase seen with prorenin alone. PAI-1 protein increased 2.75-fold. These effects were blocked by treatment with siRNA + saralasin. We conclude that prorenin at high concentration binds the (p)RR on VSMCs and is activated. This activation leads to increased expression of PAI-1 via ANG II-independent and -dependent mechanisms. These data provide a mechanism by which elevated prorenin levels in diabetes may contribute to the progression of fibrotic disease.

Retinoids Induce the PAI-1 Gene Expression Through Tyrosine Kinase-Dependent Pathways in Vascular Smooth Muscle Cells

2002 ◽  
Vol 39 (4) ◽  
pp. 503-512 ◽  
Author(s):  
Atai Watanabe ◽  
Hiroyoshi Kanai ◽  
Masashi Arai ◽  
Kenichi Sekiguchi ◽  
Tsuyoshi Uchiyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Tyrosine Kinase ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Pai 1

scholarly journals P2Y Receptor Regulation of PAI-1 Expression in Vascular Smooth Muscle Cells

2000 ◽  
Vol 20 (3) ◽  
pp. 866-873 ◽  
Author(s):  
Julie L. Bouchie ◽  
Hong-Chi Chen ◽  
Rebbeca Carney ◽  
J. Courtney Bagot ◽  
Peter A. Wilden ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Receptor Regulation ◽  
P2y Receptor ◽  
Pai 1
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