Connexins: Key Players in the Control of Vascular Plasticity and Function

2020 ◽  
Vol 100 (2) ◽  
pp. 525-572 ◽  
Author(s):  
Ulrich Pohl
Keyword(s):  
Smooth Muscle ◽  
Blood Vessels ◽  
Vascular System ◽  
Cell Reactivity ◽  
Cell Functions ◽  
Factor Type ◽  
Channel Dependent ◽  
Function Range ◽  
Independent Effects ◽  
And Function

Of the 21 members of the connexin family, 4 (Cx37, Cx40, Cx43, and Cx45) are expressed in the endothelium and/or smooth muscle of intact blood vessels to a variable and dynamically regulated degree. Full-length connexins oligomerize and form channel structures connecting the cytosol of adjacent cells (gap junctions) or the cytosol with the extracellular space (hemichannels). The different connexins vary mainly with regard to length and sequence of their cytosolic COOH-terminal tails. These COOH-terminal parts, which in the case of Cx43 are also translated as independent short isoforms, are involved in various cellular signaling cascades and regulate cell functions. This review focuses on channel-dependent and -independent effects of connexins in vascular cells. Channels play an essential role in coordinating and synchronizing endothelial and smooth muscle activity and in their interplay, in the control of vasomotor actions of blood vessels including endothelial cell reactivity to agonist stimulation, nitric oxide-dependent dilation, and endothelial-derived hyperpolarizing factor-type responses. Further channel-dependent and -independent roles of connexins in blood vessel function range from basic processes of vascular remodeling and angiogenesis to vascular permeability and interactions with leukocytes with the vessel wall. Together, these connexin functions constitute an often underestimated basis for the enormous plasticity of vascular morphology and function enabling the required dynamic adaptation of the vascular system to varying tissue demands.

scholarly journals Age-Dependent and -Independent Effects of Perivascular Adipose Tissue and Its Paracrine Activities during Neointima Formation

2019 ◽  
Vol 21 (1) ◽  
pp. 282 ◽  
Author(s):  
Eva Schütz ◽  
Rajinikanth Gogiraju ◽  
Maria Pavlaki ◽  
Ioannis Drosos ◽  
George S. Georgiadis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Smooth Muscle ◽  
Vascular Injury ◽  
Pcr Analysis ◽  
Aortic Tissue ◽  
Neointima Formation ◽  
Middle Aged ◽  
Perivascular Adipose Tissue ◽  
Independent Effects ◽  
And Function

Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (“middle-aged”) were compared to tissue or cells from mice aged 16 weeks (“adult”). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat.

Endothelial and Smooth Muscle Cells as Antagonists in Vascular Fibrinoysis

1975 ◽  
Author(s):  
V. Noordhoek Hegt
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Vascular System ◽  
Muscle Cells ◽  
Vascular Wall ◽  
Vasa Vasorum ◽  
Slide Technique

Endothelial plasminogen activator activity in different types of human blood vessels obtained from fifty necropsies and thirty-five biopsies was detected and localized by means of plasminogen-rich fibrin slides. Great differences in endothelial activator activity were found along and across (vasa vasorum) the wall of the human vascular system.The same blood vessels were simultaneously investigated by a modified fibrin slide technique using plasminogen-free fibrin slides covered by plasmin to detect and localize inhibition of fibrinolysis in the vascular wall. The great variation in plasmin inhibition in different vessels revealed by this “fibrin slide sandwich technique” appeared to be closely associated with the localization and number of smooth muscle cells present in the walls of the vascular system. Strong plasmin inhibition was generally found at sites which showed no activator activity with the regular fibrin slide technique, while areas with a high endothelial fibrinolytic activity mostly revealed no inhibitory capacity.These results indicate that much of the variation in endothelial fibrinolytic activity on fibrin slides is due to inhibitory effects from the surrounding smooth muscle cells rather than to variability in the plasminogen activator content of the endothelium itself.

scholarly journals Vascular smooth muscle phenotypic diversity and function

2010 ◽  
Vol 42A (3) ◽  
pp. 169-187 ◽  
Author(s):  
Steven A. Fisher
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Vascular Function ◽  
Striated Muscle ◽  
Vascular System ◽  
Mechanical Load ◽  
Phenotypic Diversity ◽  
Force Production ◽  
And Function ◽  
Muscle Contractile

The control of force production in vascular smooth muscle is critical to the normal regulation of blood flow and pressure, and altered regulation is common to diseases such as hypertension, heart failure, and ischemia. A great deal has been learned about imbalances in vasoconstrictor and vasodilator signals, e.g., angiotensin, endothelin, norepinephrine, and nitric oxide, that regulate vascular tone in normal and disease contexts. In contrast there has been limited study of how the phenotypic state of the vascular smooth muscle cell may influence the contractile response to these signaling pathways dependent upon the developmental, tissue-specific (vascular bed) or disease context. Smooth, skeletal, and cardiac muscle lineages are traditionally classified into fast or slow sublineages based on rates of contraction and relaxation, recognizing that this simple dichotomy vastly underrepresents muscle phenotypic diversity. A great deal has been learned about developmental specification of the striated muscle sublineages and their phenotypic interconversions in the mature animal under the control of mechanical load, neural input, and hormones. In contrast there has been relatively limited study of smooth muscle contractile phenotypic diversity. This is surprising given the number of diseases in which smooth muscle contractile dysfunction plays a key role. This review focuses on smooth muscle contractile phenotypic diversity in the vascular system, how it is generated, and how it may determine vascular function in developmental and disease contexts.

Microfluidics of blood in blood vessels stenosis

2016 ◽  
Vol 11 (2) ◽  
pp. 210-217 ◽  
Author(s):  
A.T. Akhmetov ◽  
A.A. Valiev ◽  
A.A. Rakhimov ◽  
S.P. Sametov ◽  
R.R. Habibullina
Keyword(s):  
Blood Flow ◽  
Blood Vessels ◽  
Hydraulic Resistance ◽  
Microfluidic Device ◽  
Human Body ◽  
Vascular System ◽  
Hydrodynamic Conditions ◽  
Microstructure Change ◽  
Healthy Part

It is mentioned in the paper that hydrodynamic conditions of a flow in blood vessels with the stenosis are abnormal in relation to the total hemodynamic conditions of blood flow in a vascular system of a human body. A microfluidic device developed with a stepped narrowing for studying of the blood flow at abnormal conditions allowed to reveal blood structure in microchannels simulating the stenosis. Microstructure change is observed during the flow of both native and diluted blood through the narrowing. The study of hemorheological properties allowed us to determine an increasing contribution of the hydraulic resistance of the healthy part of the vessel during the stenosis formation.

Effect of all-trans retinoic acid and pentagalloyl glucose on smooth muscle cell elastogenesis

2021 ◽  
pp. 1-13
Author(s):  
Kaveh Sanaei ◽  
Sydney Plotner ◽  
Anson Oommen Jacob ◽  
Jaime Ramirez-Vick ◽  
Narendra Vyavahare ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Retinoic Acid ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Muscle Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Tissue Engineered Blood Vessels ◽  
Pentagalloyl Glucose ◽  
Vitamin A Derivative

BACKGROUND: The main objective of tissue engineering is to fabricate a tissue construct that mimics native tissue both biologically and mechanically. A recurring problem for tissue-engineered blood vessels (TEBV) is deficient elastogenesis from seeded smooth muscle cells. Elastin is an integral mechanical component in blood vessels, allowing elastic deformation and retraction in response to the shear and pulsatile forces of the cardiac system. OBJECTIVE: The goal of this research is to assess the effect of the vitamin A derivative all-trans retinoic acid (RA) and polyphenol pentagalloyl glucose (PGG) on the expression of elastin in human aortic smooth muscle cells (hASMC). METHODS: A polycaprolactone (PCL) and the gelatin polymer composite was electrospun and doped with RA and PGG. The scaffolds were subsequently seeded with hASMCs and incubated for five weeks. The resulting tissue-engineered constructs were evaluated using qPCR and Fastin assay for their elastin expression and deposition. RESULTS: All treatments showed an increased elastin expression compared to the control, with PGG treatments showing a significant increase in gene expression and elastin deposition.

scholarly journals Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure

2008 ◽  
Vol 6 (32) ◽  
pp. 293-306 ◽  
Author(s):  
A Valentín ◽  
L Cardamone ◽  
S Baek ◽  
J.D Humphrey
Keyword(s):  
Smooth Muscle ◽  
Continuum Theory ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Rates Of Change ◽  
Biomechanical Loading ◽  
Smooth Muscle Proliferation ◽  
And Function ◽  
Diverse Data ◽  
Induced Changes

Arteries exhibit a remarkable ability to adapt to sustained alterations in biomechanical loading, probably via mechanisms that are similarly involved in many arterial pathologies and responses to treatment. Of particular note, diverse data suggest that cell and matrix turnover within vasoaltered states enables arteries to adapt to sustained changes in blood flow and pressure. The goal herein is to show explicitly how altered smooth muscle contractility and matrix growth and remodelling work together to adapt the geometry, structure, stiffness and function of a representative basilar artery. Towards this end, we employ a continuum theory of constrained mixtures to model evolving changes in the wall, which depend on both wall shear stress-induced changes in vasoactive molecules (which alter smooth muscle proliferation and synthesis of matrix) and intramural stress-induced changes in growth factors (which alter cell and matrix turnover). Simulations show, for example, that such considerations help explain the different rates of experimentally observed adaptations to increased versus decreased flows as well as differences in rates of change in response to increased flows or pressures.

An In Vitro Study of Nano-fiber Polymers for Guided Vascular Regeneration

2001 ◽  
Vol 711 ◽  
Author(s):  
Derick C. Miller ◽  
Anil Thapa ◽  
Karen M. Haberstroh ◽  
Thomas J. Webster
Keyword(s):  
Smooth Muscle ◽  
Cell Adhesion ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Surrounding Tissue ◽  
Arterial Smooth Muscle Cell ◽  
Arterial Smooth Muscle ◽  
Cell Functions ◽  
Fiber Dimensions

ABSTRACTBiomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also the dimensions of the associated nano-structured extra-cellular matrix (ECM) components. The goal of this research was to use these ideals to develop a synthetic, nano-structured, polymeric biomaterial that has cytocompatible and mechanical behaviors similar to that of natural vascular tissue. In a novel manner, poly-lactic acid/polyglycolic acid (PLGA) (50/50 wt.% mix) and polyurethane were separately synthesized to possess a range of fiber dimensions in the micron and nanometer regime. Preliminary results indicated that decreasing fiber diameter on both PLGA and PU enhanced arterial smooth muscle cell adhesion; specifically, arterial smooth muscle cell adhesion increased 23% when PLGA fiber dimensions decreased from 500 to 50 nm and increased 76% on nano-structured, compared to conventional structured, polyurethane. However, nano-structured PLGA decreased endothelial cell adhesion by 52%, whereas adhesion of these same cells was increased by 50% on polyurethane. For these reasons, the present in vitro study provides the first evidence that polymer fiber dimensions can be used to selectively control cell functions for vascular prosthesis.

scholarly journals KCNJ11 knockout morula re-engineered by stem cell diploid aggregation

2008 ◽  
Vol 364 (1514) ◽  
pp. 269-276 ◽  
Author(s):  
Timothy J Nelson ◽  
Almudena Martinez-Fernandez ◽  
Andre Terzic
Keyword(s):  
Metabolic Flux ◽  
Ex Vivo ◽  
Gene Knockout ◽  
Embryonic Stem ◽  
Adaptive Behaviour ◽  
Wild Type ◽  
New Paradigm ◽  
Cell Functions ◽  
Dependent Cell ◽  
Channel Dependent

KCNJ11 -encoded Kir6.2 assembles with ATP-binding cassette sulphonylurea receptors to generate ATP-sensitive K + (K ATP ) channel complexes. Expressed in tissues with dynamic metabolic flux, these evolutionarily conserved yet structurally and functionally unique heteromultimers serve as high-fidelity rheostats that adjust membrane potential-dependent cell functions to match energetic demand. Genetic defects in channel subunits disrupt the cellular homeostatic response to environmental stress, compromising organ tolerance in the adult. As maladaptation characterizes malignant K ATP channelopathies, establishment of platforms to examine progression of K ATP channel-dependent adaptive behaviour is warranted. Chimeras provide a powerful tool to assay the contribution of genetic variance to stress intolerance during prenatal or post-natal development. Here, KCNJ11 K ATP channel gene knockout↔wild-type chimeras were engineered through diploid aggregation. Integration of wild-type embryonic stem cells into zona pellucida-denuded morula derived from knockout embryos achieved varying degrees of incorporation of stress-tolerant tissue within the K ATP channel-deficient background. Despite the stress-vulnerable phenotype of the knockout, ex vivo derived mosaic blastocysts tolerated intrauterine transfer and implantation, followed by full-term embryonic development in pseudopregnant surrogates to produce live chimeric offspring. The development of adult chimerism from the knockout↔wild-type mosaic embryo offers thereby a new paradigm to probe the ecogenetic control of the K ATP channel-dependent stress response.

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