Clinical Hemorheology and Microcirculation - Volume 33, issue 3
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Clinical Hemorheology and Microcirculation, a peer-reviewed international scientific journal, serves as an aid to understanding the flow properties of blood and the relationship to normal and abnormal physiology. The rapidly expanding science of hemorheology concerns blood, its components and the blood vessels with which blood interacts. It includes perihemorheology, i.e., the rheology of fluid and structures in the perivascular and interstitial spaces as well as the lymphatic system. The clinical aspects include pathogenesis, symptomatology and diagnostic methods, and the fields of prophylaxis and therapy in all branches of medicine and surgery, pharmacology and drug research.
The endeavour of the Editors-in-Chief and publishers of
Clinical Hemorheology and Microcirculation is to bring together contributions from those working in various fields related to blood flow all over the world. The editors of
Clinical Hemorheology and Microcirculation are from those countries in Europe, Asia, Australia and America where appreciable work in clinical hemorheology and microcirculation is being carried out. Each editor takes responsibility to decide on the acceptance of a manuscript. He is required to have the manuscript appraised by two referees and may be one of them himself. The executive editorial office, to which the manuscripts have been submitted, is responsible for rapid handling of the reviewing process.
Clinical Hemorheology and Microcirculation accepts original papers, brief communications, mini-reports and letters to the Editors-in-Chief. Review articles, providing general views and new insights into related subjects, are regularly invited by the Editors-in-Chief. Proceedings of international and national conferences on clinical hemorheology (in original form or as abstracts) complete the range of editorial features.
The following professionals and institutions will benefit most from subscribing to
Clinical Hemorheology and Microcirculation: medical practitioners in all fields including hematology, cardiology, geriatrics, angiology, surgery, obstetrics and gynecology, ophthalmology, otology, and neurology. Pharmacologists, clinical laboratories, blood transfusion centres, manufacturing firms producing diagnostic instruments, and the pharmaceutical industry will also benefit.
Important new topics will increasingly claim more pages of
Clinical Hemorheology and Microcirculation: the role of hemorheological and microcirculatory disturbances for epidemiology and prognosis, in particular regarding cardiovascular disorders, as well as its significance in the field of geriatrics. Authors and readers are invited to contact the editors for specific information or to make suggestions.
Abstract: Cell function usually requires an accurate control of attachment to and detachment from many other cells or biological surfaces. This is usually achieved by a combination of multiple cell processes the relative importance of which may be difficult to assess. The aim of this review is to discuss the role of different mechanisms used to control adhesion on the basis of selected examples and recently developed methodologies allowing quantitative study of cell adhesion. It is concluded that cells control adhesion by modifying (i) adhesion receptor expression, as a consequence of exocytosis, endocytosis, or proteolytic mechanisms, (ii) adhesion receptor intrinsic activity,…through a variety of conformational changes, (iii) receptor organisation in cell membranes, as a consequence of topographical distribution and clustering, lateral mobility, and strength of anchoring to the cytoskeleton, and (iv) general processes unrelated to a specific receptors, such as glycocalyx changes or modification of cell shape or surface mechanical properties.
Abstract: This article provides a very brief overview of how some major mechanical properties of biological tissue and their substitutes can be described and quantified in basic form in order to understand their physiological functioning from the viewpoint of tissue regeneration, then allowing new developments in tissue engineering. After shortly reviewing the main rheological properties we have focused on the related phenomena of mass and momentum transport through tissue, considering the poroelastic characteristics of these media. Using very rough approach, it is shown how the biphasic nature of these media can influence mechanical stresses and nutriment feeding of the imbedded cells.
Abstract: Under the influence of heart and elasticity of arteries, circulating blood constantly acts upon the layers of the vessels, covered by active endothelial cells. The shear stress appears like the most efficient mechanical factor developing a rubbing physical force, the laminar flow. But pulsating and centrifugal forces allow shear to be often unsteady. Mechanobiology investigates receptors and transduction across wall cells, showing that thousands of genes are activated in the endothelium leading to a lot of adaptable functions. Atherosclerosis is due to disturbances of laminar flow in specific areas where low shear allows white cells to adhere and migrate, permeability…to increase. Coronaropathies, cerebral vascular accidents, aneurisms are so geometrically local diseases, of which lesions are subsequently enhanced by risk factors. Chronic venous insufficiency is also related to physical forces: hydrostatic and centrifugal pressures, and disruption of shear stress along the wall and around valvulae. Here also similar cells and biochemical phenomenons are the cause of wall remodelling and varicose. At the level of microcirculation the shear stress fall induces hypoxia, accumulation of white cells and hemorheological disorders in microvenulae. This leads to lesions of tissue, small vessel and ulcers. Numerous treatments in vascular diseases tend to restore flow and blood shearing. However a better understanding in the future should open new therapeutic fields and genetic approaches.
Abstract: Small-diameter prosthetic cardiovascular bypass grafts have high occlusion rates. Thrombogenicity caused by the lack of endothelial cells (ECs) on the luminal surface of the grafts is one of the main reasons for its occlusion. One strategy to improve the clinical performance of cardiovascular prosthetic grafts has been to seed its luminal surface with a monolayer of the patient's own ECs. In this strategy a “two stage” seeding procedure is utilized whereby cells obtained from a vein are amplified in cell culture, then seeded onto a fibrin–arginine–glycine–aspartate (RGD) tripeptide-enriched expanded polytetrafluoroethylene (ePTFE) graft in a rotating bioreactor for one week, after…which it is surgically implanted. This achieves patency rates approaching those of vein grafts. The disadvantage of two stage seeding is that it requires culture facilities, a large amount of RGD, which is expensive and is confined to elective cases because of the delay between cell cultivation, seeding, and graft implantation. A single stage seeding using freshly extracted ECs that is transplanted onto the graft at the same time frame of the bypass operation without the need for cell cultivation would be an ideal answer for the disadvantages of two stage seeding. Animal trials have been successful but human trials of single stage seeding have been disappointing. It has been hypothesized that extracted ECs are scarce, furthermore, they are washed off the graft surface once exposed to blood flow. This review examines the various techniques/technologies to improve endothelial cell extraction from various sources and retention onto the luminal surface of prosthetic cardiovascular grafts in order to develop a clinically applicable strategy for single stage seeding.
Abstract: The replacement of arteries with synthetic vascular prostheses often leads to failure when small-diameter or low-flow locations are concerned, due in part to the thrombogenicity of the graft surface. In order to improve long-term patency of these grafts, the concept of endothelial cell seeding has been suggested, the composite structure resulting from the combination of biologically active cells to prosthetic materials thus creating more biocompatible vascular substitutes. To achieve endothelialization of synthetic grafts, previous efforts aimed at “one-stage” procedure in the 1980's seemed clinically feasible but results of reported clinical trials were controversial and mostly disappointing. An alternative method is…an in vitro complete and preformed endothelial lining at the time of implantation: the “two-stage” procedure which implies harvest and culture of autologous endothelial cells. Up to date, the latter approach demonstrated its superiority in terms of significantly increased patency of the grafts that underwent endothelialization several years earlier.
Abstract: The study of mechanical properties of the arterial wall is an important step in the comprehension of the vascular physiopathological functioning. However, cryopreserving biological tissues using very low temperatures can induce biological and structural modifications which may involve complications (dilatation, bursting, stenosis) after reimplantation. Many procedures of mechanical tests (traction, dilatation) developped in research allow us to comprehend and analyse rheological behaviour of the arterial wall. The study presented in this article offers a new perspective to detect changes of mechanical properties of cryopreserved arterial samples. In fact, the original idea is to couple a mechanical test bed (uniaxial traction…of arterial rings) with spectroscopic measurements (autofluorescence) for the purpose of correlating mechanical modifications and spectral variations. Ultimately, this new approach could lead to develop a device allowing atraumatic and contactless optical examinations of arterial graft to determine its mechanical state before reimplantation.
Abstract: We studied the effect of mechanical forces (shear stress) on the kinetics of internalization of native LDL and ox-LDL in endothelial cell line ECV304. This study was performed by using Confocal microscopy and FRET with two carbocyanine dyes, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiO) as the donor and 3,3′-dioctadecyloxacarbocyanine perchlorate (DiI) as the receptor. The cells were incubated with a culture medium containing either 10 μg/ml DiI-LDL or DiO-LDL in static conditions or subjected to a laminar flow under a Confocal Laser Scanning Microscope (SP2 Leica, Germany). The results showed: (1) the possibility to evaluate the kinetics of LDL endocytosis in living cells,…(2) shear stress in comparison with control group more effectively enhanced LDL uptake, (3) ox-LDL (>50 μg/ml) >4 hours incubation was found to affect the cells as reflected by their detachment at low shear stress.
Keywords: Atherosclerosis, low density lipoproteins, shear stress, confocal microscopy, kinetics
Abstract: The aim of this work was to study the influences of Ca2+ (medium free calcium, with BAPTA, with 100 mM Ca2+ , 100 mM Ca2+ +10 μM ionomycin) on the expression of caveolin-1 (structural protein of caveolae) of endothelial cells (ECs) submitted to mechanical forces (shear stress) or biochemical stimulation (TNF-α). We found that shear stress enhanced the caveolin-1 expression. Simultaneously, the caveolin-1 expression is dependant on [Ca2+ ]i: [Ca2+ ]free medium+100 μM BAPTA <[Ca2+ ]free medium <[Ca2+ ]100 mM <[Ca2+ ]100 mM+10 μM ionomycin . In contrast, TNF-α induced a decrease of caveolin-1 in the cells, whatever the…[Ca2+ ]i. These results suggest that there could be a synergistic effect between shear stress and Ca2+ on caveolin-1 expression but an inflammatory stimulation (TNF-α) induces a down regulation of caveolin-1 expression.
Abstract: Recent experimental and clinical studies have shown that autologous cell based therapy using skeletal myoblasts or bone marrow-derived stem cells might have beneficial effects in chronic ischemic heart disease. The underlying concept is based on the repopulation of necrotic tissue by either readily contractile myoblasts or by bone marrow-derived stem cells. However, there is a need to resolve a number of issues for determining the better way to perform these treatments and, moreover, for assessing the real beneficial functional effect of each of these cell therapies. In this mini-review, we will discuss (i) the issues of the selection of chronic…infarct animal to truly determine the impact of cell therapy on cardiac function recovery, and (ii) the evaluation of the bio-availability and the bio-distribution of transplanted cells. Some new investigational methodologies based on clinical end-points are also proposed.
Abstract: The surface modification using thin polyelectrolyte multilayered films was proposed as a new scaffold material for different cell lines. In this study, we evaluated the possible use of polyelectrolyte multilayers as surface modification for the development of endothelial cells. In order to control the behaviour of endothelial cells, cell viability by MTT assay was studied. Moreover, the endothelial cell phenotype was checked and the expression of a leukocyte adhesion molecule (ICAM-1) was quantified. The behaviour of the cells on two polyelectrolyte multilayers was compared to cells on polystyrene, and two polyelectrolyte monolayers (terminating the multilayer architectures). The results have shown…a better cell viability on the polyelectrolyte multilayers, inducing a higher cell number compared to polyelectrolyte monolayers after 1 and 3 days of culture. Moreover, the cells showed a normal morphology of cytoskeleton. The phenotype of the endothelial cells was kept and a low level of leukocyte adhesion molecules was observed. In conclusion, the polyelectrolyte multilayers can be considered as a potential surface modification procedure to enhance the development of endothelial cells on hydrophobic substrate and which can be applied to vascular tissue engineering.
Abstract: Using Magnetic Twisting Cytometry (MTC) technique, we attempted to characterize in vitro the rigidity of the lining tissue covering the lung alveolar wall from its apical face. We purposely used a cellular model constituted by a monolayer of human alveolar epithelial cell (A549) over which microbeads, fixed to InterCellular Adhesion Molecule (ICAM-1), exert a controlled mechanical stress. ICAM-1 expression was induced by Tumor Necrosis Factor-α (TNF-α). Rigidity measurements, performed in the course of cytochalasin D depolymerization, reveal the force transmitter role of the transmembrane receptor ICAM-1 and demonstrate that ICAM-1 and F-actin linkages confers mechanical rigidity to the apical face…of the epithelial cell monolayer resembling that provided by integrins. These results confirm the ability of MTC in identifying transmembrane mechanoreceptors in relation with F-actin. Molecular linkages between ICAM-1 and F-actin were observed by spatial visualisations of the structure after double staining of F-actin and anti ICAM-1 antibody through confocal microscopy.
Keywords: Alveolar epithelial cell line, cell mechanics, F-actin structure, ICAM-1, transient magnetic bead twisting cytometry, migration, adhesion, 3D visualisation, cytoskeleton
Abstract: In this work, we investigated a voltage-sensitive fluorescent system to monitor membrane potential by spectral and lifetime fluorescence microscopy. A two-component FRET sensor has been designed that utilizes fluorescent phospholipids acceptor (DHPE-TRITC) bound on one side of the membrane and donor molecules (oxonol) which are sensitive to membrane potential. We used multiphoton excitation and FLIM to deliver contrast lifetimes of different line cancerous cells. These results provide new information concerning the differential response to depolarized cancerous cells from resting cells when compared to fibroblast normal cells. Given the sensitivity and the fast time response, this FRET system may be particularly…useful for applications involving compression of tissues by mechanical forces.
Keywords: Potentiometric dyes, FLIM, spectral, oxonol, valinomycin, fluorescence resonance energy transfer
Abstract: For more than thirty years the thrombogenicity of blood-contacting materials has been deplored. This impotency, combined with inappropriate mechanical properties of these materials, explains the poor patency of medium-sized arterial prostheses and the lack of substitutes for small diameter arteries (∅≤5 mm). The author here recalls several studies, among many others, which have opened opportunities to improve this situation. However there is a gap which has not been jumped over yet between laboratory experiments and the availability of devices which could be clinically tried. This step clearly needs strong investments from the industry people, and the latter should be encouraged…to do so by the public health authorities, as far as they believe that innovation is the condition of therapeutic progress as well as social and economic benefits.