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.

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 An integrin receptor on normal and thrombasthenic platelets that binds thrombospondin [see comments]

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2022-2027 ◽  
Author(s):  
J Lawler ◽  
RO Hynes
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Melanoma Cells ◽  
Human Platelets ◽  
Alpha Subunit ◽  
Adhesive Proteins ◽  
Alpha V Beta 3

Abstract The members of the integrin family of membrane glycoprotein heterodimer complexes function as cell surface receptors for adhesive proteins. We report here on the identification of two integrins on the surface of human platelets that bind to thrombospondin. When platelet membrane proteins are radiolabeled with 125I-lactoperoxidase, solubilized in n- octylglucoside, (Boehringer Mannheim Biochemicals, Indianapolis, IN), and applied to a column of thrombospondin-Sepharose, both complexes are bound to the column and specifically eluted with the peptide GRGDSP. One of these integrins, glycoprotein (GP) IIb-IIIa, appears to bind relatively weakly. The second integrin shares the same beta subunit (beta 3 or GPIIIa), but has a distinct alpha subunit that comigrates with the alpha subunit (alpha v) of the vitronectin receptor (VnR) on endothelial cells and reacts with a monoclonal antibody, LM142, which was raised against an integrin from M21 melanoma cells. The alpha v beta 3 integrin is present on a variety of cell types and appears to act as a receptor for thrombospondin on endothelial and smooth muscle cells. On endothelial and M21 melanoma cells this receptor is also involved in adhesion to fibrinogen, vitronectin, and von Willebrand factor (vWF). The alpha v beta 3 integrin is present at approximately equal levels on normal and thrombasthenic platelets, whereas levels of GPIIb-IIIa are greatly reduced on thrombasthenic platelets. The alpha v beta 3 integrin on thrombasthenic platelets also binds to thrombospondin-Sepharose and can be eluted with the peptide GRGDSP. These data indicate that the alpha v beta 3 integrin on platelets, endothelial cells, and smooth muscle cells functions as an Arg-Gly-Asp (RGD)-dependent receptor for thrombospondin.

The Proadhesive Properties of Multimerin in Supporting Cellular Adhesion: Evidence for RGD and Non-RGD Dependent Adhesive Mechanisms.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3917-3917
Author(s):  
Frederic Adam ◽  
Shilun Zheng ◽  
Nilesh Joshi ◽  
Youko Suehiro ◽  
David S. Kelton ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Structural Features ◽  
Cellular Adhesion ◽  
Cellular Activation ◽  
Rgd Sequence ◽  
Rgd Site

Abstract Multimerin is a large soluble protein, with an uncertain function, found in platelets, megakaryocytes, endothelium and extracellular matrix fibers but not in plasma. The observation that multimerin contains structural features of an adhesive protein, including an Arg-Gly-Asp (RGD) sequence, led us to investigate its ability to support adhesion of platelets, megakaryocytes, endothelial cells and other cell types. Multimerin had the ability to support the adhesion of both platelets and megakaryocytes and this required cellular activation and the multimerin RGD site. Studies of normal and Glanzmann platelets indicated that multimerin interacted with the major platelet integrin receptor, αIIbβ3 and radioimmunoprecipitation analyses confirmed that multimerin bound to αIIbβ3. Multimerin also supported adhesion of endothelial cells, neutrophils and other cells including smooth muscle cells, fibroblast cells, human embryonic kidney (HEK293) and epithelial cells. Unlike platelets, these cells do not express αIIbβ3; this indicated that other integrin or non-integrin receptors could be involved in cellular adhesion to multimerin. Comparisons of cell adhesion to wild-type and RGE-multimerin indicated that unlike platelets and megakaryocytes, some other cell types (e.g. endothelial cells, smooth muscle cells and neutrophils) were capable of adhering to RGE-multimerin. This suggested that cellular adhesion to multimerin occurs by both RGD and non-RGD dependent mechanisms. Finally, unlike platelets, megakaryocytes and neutrophils, adhesion of other cell types to multimerin did not require cellular activation. In conclusion, our data indicate multimerin has fairly broad proadhesive properties, involving RGD and non-RGD dependent mechanisms, and that cellular receptors including αIIbβ3 interact with multimerin to mediate its binding to activated platelets, endothelial cells and potentially other cell types.

scholarly journals Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors.

1988 ◽  
Vol 107 (6) ◽  
pp. 2351-2361 ◽  
Author(s):  
J Lawler ◽  
R Weinstein ◽  
R O Hynes
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Attachment ◽  
Solid Phase ◽  
Rat Kidney ◽  
Muscle Cells ◽  
Cell Types ◽  
Adhesive Properties ◽  
Adhesive Proteins

Thrombospondin is a 420,000-D glycoprotein that has recently been shown to have several properties in common with the members of a class of adhesive proteins. To characterize further the adhesive properties of thrombospondin, we have studied its ability to support cell attachment. Thrombospondin adsorbed to plastic dishes supports the attachment of human endothelial and smooth muscle cells and the monocyte-like cell line (U937) as well as normal rat kidney cells. The majority of attached cells do not spread on the solid-phase thrombospondin. The attachment of all four cell types to thrombospondin is abolished if the assay is performed in the presence of EGTA, although the cells still attach to fibronectin. If thrombospondin is adsorbed to the dishes in the presence of EGTA and then washed with buffer containing calcium before addition of the cells, attachment is still markedly inhibited, indicating that calcium affects the conformation and function of thrombospondin. Attachment of all four cell types is also markedly inhibited by the synthetic peptides gly-arg-gly-asp-ser-pro (GRG-DSP) and gly-arg-gly-asp-ala-cys (GRGDAC) but not by the control peptide gly-arg-gly-glu-ser-pro (GRG-ESP). Affinity chromatography of n-octylglucoside extracts of surface-labeled endothelial cells or smooth muscle cells on thrombospondin-Sepharose and GRG-DSP-Affigel columns was used to identify an integrin complex related to glycoprotein IIb-IIIa as an RGD-dependent receptor for thrombospondin. In addition, a monoclonal antibody (LM609) that blocks attachment of endothelial cells to vitronectin, fibrinogen, and von Willebrand factor also inhibits attachment of endothelial cells to thrombospondin. These data indicate that the attachment of cells to thrombospondin is mediated by RGD and calcium-dependent mechanisms and is consistent with the hypothesis that the GRGDAC sequence in thrombospondin is a site for interaction with an integrin receptor of the beta 3 subclass.

Stem Cells and Vascular Regenerative Medicine

2008 ◽  
Author(s):  
Taby Ahsan ◽  
Adele M. Doyle ◽  
Garry P. Duffy ◽  
Frank Barry ◽  
Robert M. Nerem
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Regenerative Medicine ◽  
Blood Vessel ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
In Vitro Proliferation ◽  
The Impact ◽  
Blood Vessel Substitutes

Vascular applications in regenerative medicine include blood vessel substitutes and vasculogenesis in ischemic or engineered tissues. For these repair processes to be successful, there is a need for a stable supply of endothelial and smooth muscle cells. For blood vessel substitutes, the immediate goal is to enable blood flow, but vasoactivity is necessary for long term success. In engineered vessels, it is thought that endothelial cells will serve as an anti-thrombogenic lumenal layer, while smooth muscle cells contribute to vessel contractility. In other clinical applications, what is needed is not a vessel substitute but the promotion of new vessel formation (vasculogenesis). A simplified account of vasculogenesis is that endothelial cells assemble to form vessel-like structures that can then be stabilized by smooth muscle cells. Overall, the need for new vasculature to transfer oxygen and nutrients is important to reperfuse not only ischemic tissue in vivo, but also dense, structurally complex engineered tissue. The impact of these vascular therapies, however, is limited in part by the low yield and inadequate in vitro proliferation potential of primary endothelial and smooth muscle cells. Thus, there is a need to address the cell sourcing issue for vascular cell-based therapies, potentially using stem cells.

scholarly journals Cultured endothelial cells produce heparinlike inhibitor of smooth muscle cell growth

1981 ◽  
Vol 90 (2) ◽  
pp. 372-379 ◽  
Author(s):  
JJ Castellot ◽  
ML Addonizio ◽  
R Rosenberg ◽  
MJ Karnovsky
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cell Growth ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Chondroitin Sulfate ◽  
Conditioned Medium ◽  
Muscle Cell ◽  
Muscle Cells ◽  
Smooth Muscle Cell Growth

Using cultured cells from bovine and rat aortas, we have examined the possibility that endothelial cells might regulate the growth of vascular smooth muscle cells. Conditioned medium from confluent bovine aortic endothelial cells inhibited the proliferation of growth-arrested smooth muscle cells. Conditioned medium from exponential endothelial cells, and from exponential or confluent smooth muscle cells and fibroblasts, did not inhibit smooth muscle cell growth. Conditioned medium from confluent endothelial cells did not inhibit the growth of endothelial cells or fibroblasts. In addition to the apparent specificity of both the producer and target cell, the inhibitory activity was heat stable and not affected by proteases. It was sensitive flavobacterium heparinase but not to hyaluronidase or chondroitin sulfate ABC lyase. It thus appears to be a heparinlike substance. Two other lines of evidence support this conclusion. First, a crude isolate of glycosaminoglycans (TCA-soluble, ethanol-precipitable material) from endothelial cell-conditioned medium reconstituted in 20 percent serum inhibited smooth muscle cell growth; glycosaminoglycans isolated from unconditioned medium (i.e., 0.4 percent serum) had no effect on smooth muscle cell growth. No inhibition was seen if the glycosaminoglycan preparation was treated with heparinase. Second, exogenous heparin, heparin sulfate, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate ABC, and hyaluronic acid were added to 20 percent serum and tested for their ability to inhibit smooth muscle cell growth. Heparin inhibited growth at concentrations as low as 10 ng/ml. Other glycosaminoglycans had no effect at doses up to 10 μg/ml. Anticoagulant and non- anticoagulant heparin were equally effective at inhibiting smooth muscle cell growth, as they were in vivo following endothelial injury (Clowes and Karnovsk. Nature (Lond.). 265:625-626, 1977; Guyton et al. Circ. Res. 46:625-634, 1980), and in vitro following exposure of smooth muscle cells to platelet extract (Hoover et al. Circ. Res. 47:578-583, 1980). We suggest that vascular endothelial cells may secrete a heparinlike substance in vivo which may regulate the growth of underlying smooth muscle cells.

Abstract 180: The Myristolated Alanine-Rich C Kinase Substrate (MARCKS) Differentially Regulates Proliferation of Vascular Smooth Muscle Cells and Endothelial Cells through Affecting Protein Stability and Proteolytic Processing of the Kinase Interacting with Stathmin (KIS)

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dan Yu ◽  
Charles Drucker ◽  
Rajabrata Sarkar ◽  
Dudley K Strickland ◽  
Thomas S Monahan
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Protein Stability ◽  
Muscle Cells ◽  
Cell Types ◽  
Proteolytic Processing ◽  
Functional Domain ◽  
Human Coronary Artery

Objective: Presently, the antiproliferative agents used in drug eluting stents and drug coated balloons inhibit both VSMC and endothelial cell (EC) proliferation, and thus these patients require dual antiplatelet therapy indefinitely. Identification of a VSMC-specific target to prevent proliferation represents a significant unmet clinical need. Previously we found that knockdown of MARCKS arrests VSMC proliferation through a p27 kip1 -dependent mechanism. Interestingly MARCKS knockdown increases EC proliferation. p27 kip1 is phosphorylated by KIS allowing it to exit the nucleus and be degraded. Here we seek to understand how MARCKS influences KIS protein expression in these two cell types. Approach and Results: We performed siRNA-mediated knock down of MARCKS in human coronary artery endothelial cells (CAECs) and human coronary artery smooth muscle cells (CASMCs). MARCKS knockdown did not affect KIS mRNA expression as determined with RT-PCR in either cell type. KIS protein stability was evaluated in the presence of cyclohexamide with Western blot. In CAECs, MARCKS knockdown increased KIS stability, however, in CASMCs, MARCKS knockdown significantly decreased KIS protein stability. In CASMCs, MARCKS knockdown significantly increased KIS ubiquitinization where as in CAECs, MARCKS knockdown decreased KIS ubiquitinization. Interestingly, the well-studied functional domain of MARCKS(ED domain) is not directly involved in KIS regulation. MARCKS mutants (S4G and S4D) rescued proliferation in VSMCs. MARCKS knockdown in vivo in the murine femoral wire injury model resulted in decreased medial bromodeoxyuridine (BrdU) integration and neointima formation. MARCKS knockdown enhanced endothelial barrier function recovery four days after injury as assessed by Evans Blue integration. Conclusions: MARCKS differentially regulates the protein stability and proteolytic processing of KIS in VSMCs and ECs. The differential interaction of MARCKS and KIS likely explains the observed difference in proliferation observed with MARCKS knockdown in these two cell types.

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.

Smooth muscle cells alter endothelial cell regulation of smooth muscle cell migration

2000 ◽  
Vol 191 (4) ◽  
pp. S3
Author(s):  
Peter R Nelson ◽  
Arthur J Kehas ◽  
Robert J Wagner ◽  
Richard R Proia ◽  
Jack L Cronenwett ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Muscle Cells ◽  
Cell Regulation ◽  
Smooth Muscle Cell Migration

Comparison of ICAM-1 and VCAM-1 Expression in Various Human Endothelial Cell types and Smooth Muscle Cells

Endothelium ◽  
1998 ◽  
Vol 6 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Keiichi Kanda ◽  
G. Thomas Hayman ◽  
Matthew D. Silverman ◽  
Peter I. Lelkes
Keyword(s):  
Smooth Muscle ◽  
Endothelial Cell ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Human Endothelial Cell
Sign in / Sign up

Export Citation Format

Share Document