Requirement of the MADS-box transcription factor MEF2C for vascular development

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4565-4574 ◽  
Author(s):  
Q. Lin ◽  
J. Lu ◽  
H. Yanagisawa ◽  
R. Webb ◽  
G.E. Lyons ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Target Genes ◽  
Vascular Development ◽  
Muscle Cells ◽  
Mads Box ◽  
Vascular Plexus

The embryonic vasculature develops from endothelial cells that form a primitive vascular plexus which recruits smooth muscle cells to form the arterial and venous systems. The MADS-box transcription factor MEF2C is expressed in developing endothelial cells and smooth muscle cells (SMCs), as well as in surrounding mesenchyme, during embryogenesis. Targeted deletion of the mouse MEF2C gene resulted in severe vascular abnormalities and lethality in homozygous mutants by embryonic day 9.5. Endothelial cells were present and were able to differentiate, but failed to organize normally into a vascular plexus, and smooth muscle cells did not differentiate in MEF2C mutant embryos. These vascular defects resemble those in mice lacking the vascular-specific endothelial cell growth factor VEGF or its receptor Flt-1, both of which are expressed in MEF2C mutant embryos. These results reveal multiple roles for MEF2C in vascular development and suggest that MEF2-dependent target genes mediate endothelial cell organization and SMC differentiation.

Electrical activation of endothelium evokes vasodilation and hyperpolarization along hamster feed arteries

2001 ◽  
Vol 280 (1) ◽  
pp. H160-H167 ◽  
Author(s):  
Geoffrey G. Emerson ◽  
Steven S. Segal
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Cell Damage ◽  
Muscle Cells ◽  
Sympathetic Nerves ◽  
Retractor Muscle ◽  
Receptor Interactions ◽  
Feed Arteries

Endothelial cells are considered electrically unexcitable. However, endothelium-dependent vasodilators (e.g., acetylcholine) often evoke hyperpolarization. We hypothesized that electrical stimulation of endothelial cells could evoke hyperpolarization and vasodilation. Feed artery segments (resting diameter: 63 ± 1 μm; length 3–4 mm) of the hamster retractor muscle were isolated and pressurized to 75 mmHg, and focal stimulation was performed via microelectrodes positioned across one end of the vessel. Stimulation at 16 Hz (30–50 V, 1-ms pulses, 5 s) evoked constriction (−20 ± 2 μm) that spread along the entire vessel via perivascular sympathetic nerves, as shown by inhibition with tetrodotoxin, ω-conotoxin, or phentolamine. In contrast, stimulation with direct current (30 V, 5 s) evoked vasodilation (16 ± 2 μm) and hyperpolarization (11 ± 1 mV) of endothelial and smooth muscle cells that conducted along the entire vessel. Conducted responses were insensitive to preceding treatments, atropine, or N ω-nitro-l-arginine, yet were abolished by endothelial cell damage (with air). Injection of negative current (≤1.6 nA) into a single endothelial cell reproduced vasodilator responses along the entire vessel. We conclude that, independent of ligand-receptor interactions, endothelial cell hyperpolarization evokes vasodilation that is readily conducted along the vessel wall. Moreover, electrical events originating within a single endothelial cell can drive the relaxation of smooth muscle cells throughout the entire vessel.

scholarly journals Glycyrrhetinic derivatives inhibit hyperpolarization in endothelial cells of guinea pig and rat arteries

2002 ◽  
Vol 282 (1) ◽  
pp. H335-H341 ◽  
Author(s):  
Marianne Tare ◽  
H. A. Coleman ◽  
Helena C. Parkington
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Muscle Cells ◽  
Mesenteric Arteries ◽  
Resting Membrane Potential ◽  
Variable Effect

Glycyrrhetinic acid (GA) derivatives have been used to implicate gap junctions in vasorelaxation attributed to endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to assess whether GA compounds affect endothelial cell hyperpolarization. Membrane potentials were recorded from dye-identified endothelial and smooth muscle cells of guinea pig coronary and rat mesenteric arteries. GA derivatives had varied effects on the resting membrane potential: depolarization, hyperpolarization, or no effect, depending on the artery. 18α-GA (50 μM) had a small variable effect on ACh-induced hyperpolarizations in endothelial cells. 18β-GA (30 μM) and carbenoxolone (100 μM) significantly reduced ACh-induced hyperpolarizations in both endothelial and smooth muscle cells. Smooth muscle action potentials in rat tail arteries were smaller and slower in the presence of 18β-GA. Nerve-induced excitatory junction potentials were inhibited by 18β-GA and carbenoxolone, whereas the time course of their decay initially increased and then decreased. In conclusion, the GA compounds had a range of effects. Their inhibition of the EDHF hyperpolarization and relaxation in the smooth muscle may stem from the inhibition of endothelial cell hyperpolarization.

scholarly journals An endothelial cell-derived growth factor.

1980 ◽  
Vol 85 (2) ◽  
pp. 467-472 ◽  
Author(s):  
C Gajdusek ◽  
P DiCorleto ◽  
R Ross ◽  
S M Schwartz
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
3T3 Cells ◽  
Free Plasma ◽  
Heat Instability

Cell-free plasma-derived serum (PDS) is deficient in the platelet-derived growth factor and will not support the growth of 3T3 cells, fibroblasts, or smooth muscle cells. However, when PDS-containing medium is preincubated with endothelial cells, the medium becomes modified so that it will support growth. The activity produced by the endothelial cells results from a polypeptide of 10,000 to 30,000 daltons which has several features that differ from those of the platelet-derived growth factor, including heat instability and lack of adsorption to CM Sephadex.

scholarly journals Chlamydia pneumoniae Infection of Human Endothelial Cells Induces Proliferation of Smooth Muscle Cells via an Endothelial Cell-Derived Soluble Factor(s)

1999 ◽  
Vol 67 (6) ◽  
pp. 2909-2915 ◽  
Author(s):  
Brian K. Coombes ◽  
James B. Mahony
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Chlamydia Pneumoniae ◽  
Umbilical Vein ◽  
Muscle Cells ◽  
Cell Counting ◽  
Soluble Factor ◽  
Dose Dependent

ABSTRACT An association of Chlamydia pneumoniae with atherosclerosis and coronary heart disease has been determined epidemiologically and by the detection of C. pneumoniaeorganisms in atherosclerotic lesions in both humans and animal models of atherosclerosis. Previously, it has been shown that C. pneumoniae is capable of replicating in cell types found within atheromatous lesions, viz., endothelial cells, smooth muscle cells (SMC), and macrophages, yet the role of C. pneumoniae in the pathogenesis of atherosclerosis has not been determined. Since intimal thickening is a hallmark of atherosclerosis, we investigated whether C. pneumoniae infection of human umbilical vein endothelial cells (HUVEC) could induce the expression of a soluble factor(s) with mitogenic potential for SMC by using [3H]thymidine incorporation and direct cell counting. Conditioned medium harvested from HUVEC infected with C. pneumoniae stimulated SMC replication in a time- and dose-dependent fashion. Infection studies using various multiplicities of infection (MOIs) ranging from 0.001 to 1 demonstrated a dose-dependent production of the soluble factor(s). At an MOI of 1, SMC stimulation indices were 8.4 (P < 0.01) and 12.2 (P < 0.01) for conditioned media harvested at 24 and 48 h, respectively. To determine whether viable C. pneumoniae was required for production of the soluble factor(s), HUVEC were infected with heat-inactivated C. pneumoniae or with viable organisms in the presence of chloramphenicol. Both treatments produced stimulation indices similar to those for liveC. pneumoniae in the absence of chloramphenicol (P > 0.05), indicating that the factor(s) was produced by HUVEC and not by C. pneumoniae and that signal transduction events following chlamydia endocytosis may be important in the production of a soluble factor(s). The ability of C. pneumoniae to elicit an endothelial cell-derived soluble factor(s) that stimulates SMC proliferation may be important in the pathogenesis of atherosclerosis.

Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles

2007 ◽  
Vol 292 (4) ◽  
pp. F1124-F1131 ◽  
Author(s):  
T. R. Uhrenholt ◽  
J. Schjerning ◽  
P. M. Vanhoutte ◽  
B. L. Jensen ◽  
O. Skøtt
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
No Production ◽  
Contractile Apparatus ◽  
Afferent Arterioles

Vasoconstriction and increase in the intracellular calcium concentration ([Ca2+]i) of vascular smooth muscle cells may cause an increase of endothelial cell [Ca2+]i, which, in turn, augments nitric oxide (NO) production and inhibits smooth muscle cell contraction. This hypothesis was tested in microperfused rabbit renal afferent arterioles, using fluorescence imaging microscopy with the calcium-sensitive dye fura-2 and the NO-sensitive dye 4-amino-5-methylamino-2′,7′-difluorescein. Both dyes were loaded into smooth muscle and endothelium. Depolarization with 100 mmol/l KCl led to a transient vasoconstriction which was converted into a sustained response by N-nitro-l-arginine methyl ester (l-NAME). Depolarization increased smooth muscle cell [Ca2+]ifrom 162 ± 15 nmol/l to a peak of 555 ± 70 nmol/l ( n = 7), and this response was inhibited by 80% by the l-type calcium channel blocker calciseptine. After a delay of 10 s, [Ca2+]iincreased in endothelial cells immediately adjacent to reactive smooth muscle cells, and this calcium wave spread in a nonregenerative fashion laterally into the endothelial cell layer with a velocity of 1.2 μm/s. Depolarization with 100 mmol/l KCl led to a significant increase in NO production ([NO]i) which was inhibited by l-NAME ( n = 5). Acetylcholine caused a rapid increase in endothelial [Ca2+]i, which did not transfer to the smooth muscle cells. l-NAME treatment did not affect changes in smooth muscle [Ca2+]iafter depolarization, but it did increase the calcium sensitivity of the contractile apparatus. We conclude that depolarization increases smooth muscle [Ca2+]iwhich is transferred to the endothelial cells and stimulates NO production which curtails vasoconstriction by reducing the calcium sensitivity of the contractile apparatus.

We Have Contact: Endothelial Cell-Smooth Muscle Cell Interactions

Physiology ◽  
2014 ◽  
Vol 29 (4) ◽  
pp. 234-241 ◽  
Author(s):  
Brenda Lilly
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Endothelial Cell ◽  
Blood Vessel ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cells ◽  
Cell Types ◽  
Unique Contribution ◽  
Vessel Growth

Blood vessels are composed of two primary cell types, endothelial cells and smooth muscle cells, each providing a unique contribution to vessel function. Signaling between these two cell types is essential for maintaining tone in mature vessels, and their communication is critical during development, and for repair and remodeling associated with blood vessel growth. This review will highlight the pathways that endothelial cells and smooth muscle cells utilize to communicate during vessel formation and discuss how disruptions in these pathways contribute to disease.

Plasminogen Activator Inhibitor-1 Expression in Human Liver and Healthy or Atherosclerotic Vessel Walls

1994 ◽  
Vol 72 (01) ◽  
pp. 044-053 ◽  
Author(s):  
N Chomiki ◽  
M Henry ◽  
M C Alessi ◽  
F Anfosso ◽  
I Juhan-Vague
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Plasminogen Activator ◽  
Human Liver ◽  
Plasminogen Activator Inhibitor ◽  
Muscle Cells ◽  
Vessel Walls ◽  
Activator Inhibitor ◽  
Pai 1

SummaryIndividuals with elevated levels of plasminogen activator inhibitor type 1 are at risk of developing atherosclerosis. The mechanisms leading to increased plasma PAI-1 concentrations are not well understood. The link observed between increased PAI-1 levels and insulin resistance has lead workers to investigate the effects of insulin or triglyceride rich lipoproteins on PAI-1 production by cultured hepatocytes or endothelial cells. However, little is known about the contribution of these cells to PAI-1 production in vivo. We have studied the expression of PAI-1 in human liver sections as well as in vessel walls from different territories, by immunocytochemistry and in situ hybridization.We have observed that normal liver endothelial cells expressed PAI-1 while parenchymal cells did not. However, this fact does not refute the role of parenchymal liver cells in pathological states.In healthy vessels, PAI-1 mRNA and protein were detected primarily at the endothelium from the lumen as well as from the vasa vasorum. In normal arteries, smooth muscle cells were able to produce PAI-1 depending on the territory tested. In deeply altered vessels, PAI-1 expression was observed in neovessels scattering the lesions, in some intimal cells and in smooth muscle cells. Local increase PAI-1 mRNA described in atherosclerotic lesions could be due to the abundant neovascularization present in the lesion as well as a raised expression in smooth muscle cells. The increased PAI-1 in atherosclerosis could lead to fibrin deposit during plaque rupture contributing further to the development and progression of the lesion.

Thrombin Inhibition and Thrombin Generation by Cultured Aortic Endothelial and Smooth Muscle Cells from Minipig

1982 ◽  
Vol 48 (01) ◽  
pp. 101-103 ◽  
Author(s):  
B Kirchhof ◽  
J Grünwald
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vessel Wall ◽  
Thrombin Generation ◽  
Muscle Cells ◽  
Thrombin Inhibition ◽  
Generating Capacity ◽  
Wall Interaction ◽  
Cells Cultured

SummaryEndothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.

Vascular Smooth Muscle Cells Inhibit the Plasminogen Activators Secreted by Endothelial Cells

1985 ◽  
Vol 53 (02) ◽  
pp. 165-169 ◽  
Author(s):  
Walter E Laug
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Conditioned Medium ◽  
Vascular Smooth Muscle Cells ◽  
Inhibitory Activity ◽  
Muscle Cells ◽  
Plasminogen Activators ◽  
Bovine Endothelial Cells

SummaryTPure cultures of bovine endothelial cells (EC) produce and secrete large amounts of plasminogen activators (PA). Cocultivation of EC with vascular smooth muscle cells (SMC) resulted in a significant decrease of PA activities secreted by the EC, whereas the cellular PA activities remained unaffected. Secreted PA activities were absent in the growth medium as long as the SMC to EC ratio was 2:1 or higher. The PA inhibitory activity of the SMC was rapid and cell-to-cell contact was not necessary.The PA inhibitory activity was present in homogenates of SMC as well as in the medium conditioned by them but not in the extracellular matrix elaborated by these cells. Serum free medium conditioned by SMC neutralized both tissue type (t-PA) and urokinase like (u-PA) plasminogen activators. Gel electrophoretic analysis of SMC conditioned medium followed by reverse fibrin autography demonstrated PA inhibitory activities in the molecular weight (Mr) range of 50,000 to 52,000 similar to those present in media conditioned by bovine endothelial cells or fibroblasts. Regular fibrin zymography of SMC conditioned medium incubated with u-PA or t-PA revealed the presence of a component with a calculated approximate Mr of 45,000 to 50,000 which formed SDS resistant complexes with both types of PA.These data demonstrate that vascular SMC produce and secrete (a) inhibitor(s) of PAs which may influence the fibrinolytic potential of EC.

Sign in / Sign up

Export Citation Format

Share Document