Clinical Hemorheology and Microcirculation - Volume 37, issue 1-2

Authors: Kerdjoudj, Halima | Moby, Vanessa | Berthelemy, Nicolas | Gentils, Monique | Boura, Cédric | Bordenave, Laurence | Stoltz, Jean-François | Menu, Patrick

Article Type: Research Article

Abstract: Although autogenous vessels are useful in surgery, often patients cannot furnish suitable vessels. If there are not available, two possible alternatives for vessel replacements are to use vascular synthetic prostheses such as Dacron® and polytetrafluoroethylene (PTFE) or cryopreserved allografts. However, their success has been limited to replace small-diameter (<6 mm) arterial vessel because of their high thrombogenicity and compliance mismatch. On account of a clear clinical need for a functional arterial substitute, tissue engineering techniques have been developed. This review encompasses the use of mature endothelial, endothelial progenitor and bone marrow cells combined with natural or synthetic scaffolds whose …surface has been modified with multiple origin matrices. Show more

Keywords: Vascular tissue engineering, small-diameter vascular graft, matrix, cryopreserved arteries, endothelial cells, endothelial progenitor cells, bone marrow cells

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 89-98, 2007

Authors: Gaucher, C. | Devaux, C. | Boura, C. | Lacolley, P. | Stoltz, J.-F. | Menu, P.

Article Type: Research Article

Abstract: In the vascular system, the shear applied to the vascular wall activates mechano-sensors located on endothelial cells (ECs) leading to a modification in the gene expression profile. We applied laminar shear stress at 1 Pa on ECs for 6 h and measured by quantitative real time PCR the expression modulation of genes implied in inflammation (ICAM-1 and E-selectin), oxidative stress sensing (HO-1) and vascular tone modulation (eNOS). We showed that all these genes are shear stress inducible. ICAM-1 is more up-regulated than E-selectin suggesting different levels of implication in inflammatory responses and different modes of induction (SSRE, cytokine). Laminar shear …stress induces an oxidative stress translated into HO-1 up-regulation, and a possible vasodilatation through the induction of eNOS. Our laminar shear stress system opens a novel and interesting frame in the evaluation of the impact on ECs and blood cells of new pharmacological substances injected in the bloodstream. Show more

Keywords: Laminar shear stress, inflammation, oxidative stress, vasomotion, endothelial cells

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 99-107, 2007

Authors: Black, Stephen M. | Kumar, Sanjiv | Wiseman, Dean | Ravi, Kandasamy | Wedgwood, Stephen | Ryzhov, Victor | Fineman, Jeffrey R.

Article Type: Research Article

Abstract: An increasing number of studies implicate oxidative stress in the development of endothelial dysfunction and the pathogenesis of cardiovascular disease. Further, this oxidative stress has been shown to be associated with alterations in both the endothelin-1 (ET-1) and nitric oxide (NO) signaling pathways such that bioavailable NO is decreased and ET-1 signaling is potentiated. However, recent data, from our groups and others, have shown that oxidative stress, ET-1, and NO are co-regulated in a complex fashion that appears to be dependent on the cellular levels of each species. Thus, when ROS levels are transiently elevated, NO signaling is potentiated through …transcriptional, post-transcriptional, and post-translational mechanisms. However, in pediatric pulmonary hypertensive disorders, when reactive oxygen species (ROS) increases are sustained by ET-1 mediated activation of smooth muscle cell ETA subtype receptors, NOS gene expression and NO signaling are reduced. Further, increases in oxidative stress can stimulate both the expression of the ET-1 gene and the secretion of the ET-1 peptide. Thus, this manuscript will review the available data regarding the interaction of NO, ET-1, and ROS in the endothelial dysfunction of pediatric pulmonary hypertension. In addition, we will suggest avenues of both basic and clinical research that will be important to develop novel pulmonary hypertension treatment and prevention strategies. Show more

Keywords: Pulmonary hypertension, reactive oxygen species, enzyme inhibition, gene expression, cell signaling

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 111-120, 2007

Authors: Thacher, T. | Gambillara, V. | Da Silva, R. | Montorzi, G. | Stergiopulos, N. | Silacci, P.

Article Type: Research Article

Abstract: Shear stress has been shown to influence endothelial cell gene expression and morphology. In particular, low and bi-directional shear stress, mimicking conditions at plaque-prone areas, down-regulates the expression of several atheroprotective genes, and up-regulates that of other genes considered as pro-inflammatory. Another mechanical situation thought to have a negative influence on vascular functions is arterial stiffness. Loss of arterial compliance occurs during ageing, in diabetic as well as in hypertensive patients. In this work we investigated the effects of these two particular hemodynamic environments (bi-directional shear stress and reduced compliance), using a recently developed perfusion system allowing to expose native …arteries in vitro to complex hemodynamic environments. We were able to show that both plaque-prone shear stress and reduced compliance trigger endothelial dysfunction, but via different mechanisms. Only reduced compliance affected vascular contractility, inducing a dedifferentiation of smooth muscle cells and a consequent loss of norepinephrine sensitivity. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 121-130, 2007

Authors: Kadi, A. | de Isla, N. | Lacolley, P. | Stoltz, J.F. | Menu, P.

Article Type: Research Article

Abstract: Endothelial cells (ECs) which participate the interface between the blood and the vessel wall undergo morphologic changes in response to shear stress induced by blood flow, liable for the important regulation on physiologic and pathophysiologic function of blood vessels. Shear stress induced changes in cell morphology, begin with elongation in the direction of shearing and end by a reorientation and assembly of F-actin stress fibers. Shear stress is also implicated in many important ECs functions such as: decrease of platelet aggregation, anti-thrombogenic and anti-adhesive effects, inhibition of vascular smooth muscle cell (SMC) proliferation and regulation of their contraction and arterial …tonicity, via a regulation of vasodilator and vasoconstrictor secretion molecules such as nitric oxide (NO), endothelin I, prostacyclin and angiotensin II. Besides, many of human diseases such as hypercholesterolemia, diabetes and hypertension, are strongly linked to a disturbance of the production of several vasodilator or vasoconstrictor molecules. The aim of this in-vitro study was to evaluate the potential balance between time and rate effects of shearing in cell shape changes and e-NOS activity. Two unidirectional steady laminar flow rates (1.2 Pa and 2.0 Pa) were applied on EC monolayers, each one for a short and a long period, (6 h and 24 h). Cytoskeleton reorganization was evaluated by actin filaments labelling and observed by confocal microscopy. NO production was evaluated by a colorimetric method using the Griess reagent kit for nitrite determination. Results showed that laminar flow affected cell rearrangement by inducing cytoskeleton reorientation and increased production of NO. Laminar shear rate at 2.0 Pa for 24 h did not upregulate NO release. Whereas at 1.2 Pa for 24 h, NO release increased by 33% compared with the static conditions. Both 1.2 Pa and 2.0 Pa for 6 h increased NO release by 17% and 24% respectively as compared with the static conditions. These observations suggested that stress fiber assembly, which controls EC reorientation and NO production, are dependent on rate and time of shearing. In addition, there appear to be a relation between the cytoskeleton reorganization stage and NO production. These results could promote the parameters to evaluate the more appropriate pattern of shearing, to evaluate a potential pharmacological effect on hypertension disorder decrease. Show more

Keywords: e-NOS, Nitric oxide, ECs, SMCs, shear stress, hypertension, vasorelaxation, cytoskeleton reorganization

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 131-140, 2007

Authors: Cosentino, Francesco | Osto, Elena

Article Type: Research Article

Abstract: Aging is the major risk factor for the development of cardiovascular diseases, the leading cause of morbidity, mortality and disability in western countries. Mounting data suggest that cardiovascular structure and function change with time as result of an “aging process”, regarded as an independent process which accompanies aging, interwines and modulates superimposed traditional cardiovascular risk factors to determine the peculiar occurrence, presentations and prognosis of heart disease in the elderly. A whole body of data underlies the impairment of endothelial function due to oxidative stress as a crucial feature of the aging process acting on the cardiovascular system. Insights into …molecular and cellular mechanisms of age-associated endothelial dysfunction may provide new strategies to treat age-related cardiovascular diseases. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 143-147, 2007

Authors: Llorens, Silvia | Fernández, Ana Patricia | Nava, Eduardo

Article Type: Research Article

Abstract: We have assessed the NO system in the cardiovascular and renal systems of young, adult and old normotensive (WKY) and hypertensive rats (SHR). The NO pathway was assessed analytically, by measuring the concentration of nitrate in plasma as well as the activity of NO synthases in the left ventricle and kidney; and functionally, by measuring the isometric forces generated upon addition of the NO blocker, L-NAME, to aortic segments. All these procedures consistently revealed that the NO pathway is upregulated in hypertension or senescence. In addition, we have performed immunohistochemical studies of NO synthases in the kidney of adult animals …(WKY and SHR). NO synthases are expressed throughout the kidney in both rat strains. Immunoreactivity of neuronal NOS was higher in the tubular cells of the renal medulla of the SHR. Staining with the inducible and endothelial NOS antibodies was similar in normo- and hypertension. In summary, hypertension and ageing upregulate the NO pathway in structures involved in the regulation of blood pressure (heart, vessels and kidney). Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 149-156, 2007

Authors: Shreenivas, Satya | Oparil, Suzanne

Article Type: Research Article

Abstract: Endothelin-1 (ET-1) is a powerful vasoconstrictor and mitogen that contributes to blood pressure elevation and related vascular remodeling and target organ damage. ET-1 also influences salt and water homeostasis through effects on the renin-angiotensin-aldosterone system and vasopressin, thus elevating blood pressure and increasing vascular tone. Circulating ET-1 levels are elevated in a variety of animal models of hypertension, particularly those that are salt-dependent, and in a subset of human hypertensives, i.e. African-Americans and those with renal dysfunction. ET type B receptors, which normally have vasodilator functions, mediate vasoconstriction in some hypertensives, and hypertensive African-American patients may have increased numbers of …vasoconstrictor ET-B receptors in their vascular smooth muscle. Whether selective ET-A or combined ET-A/ET-B receptor antagonists are more efficacious in treating hypertension and related cardiovascular disease is controversial. ET antagonists have only modest BP lowering effects in the general population of essential hypertensives, but show promise in patients with severe, treatment resistant hypertension. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 157-178, 2007

Authors: Schalkwijk, Casper G. | van Dam, Bastiaan | Stehouwer, Coen D.A. | van Hinsbergh, Victor W.M

Article Type: Research Article

Abstract: Statins can protect endothelial activation independent from their lipid-lowering effects. To gain more insight in mechanisms via which HMG-CoA inhibition may attenuate endothelial activation, we assessed the effects of mevastatin on eNOS expression of non- and modified-LDL treated endothelial cells and on basal and hydrogen peroxide-induced lipid peroxidation. Oxidized-LDL (Ox-LDL), but not glycated or acylated LDL decreased eNOS expression in human endothelial cells. The extent to which Ox-LDL decreases eNOS expression depends on the extent of modification of Ox-LDL. Mevastatin increased eNOS-expression, both in the presence and absence of Ox-LDL. In addition, mevastatin decreased the H2 O2 -induced (100 μM) …lipid peroxidation in endothelial cells. This study shows that mevastatin has protective effects on endothelial cells by inducing eNOS and by inhibiting lipid peroxidation. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 179-184, 2007

Authors: Rush, James W.E. | Ford, Rebecca J.

Article Type: Research Article

Abstract: Oxidative stress contributes to homeostasis in vascular cells. However, excessive ROS is pathophysiological and contributes to impaired endothelium-dependent dilation in hypertension by decreasing NO bio-availability. NADPH oxidase is upregulated in hypertension by humoral and mechanical signals, and quantitatively this enzyme makes the largest contribution to ROS production. Genetic and chemical manipulation of NADPH oxidase and of antioxidant enzymes cause predictable changes in oxidative stress and endothelium-dependent function in hypertension. The chemical antioxidant glutathione also impacts endothelium-mediated vascular function, possibly through maintenance of S-nitrosothiols and via other independent antioxidant effects. The effects of changes in thiols and nitrosothiols on vasomotor function …in hypertension need to be examined. H2 O2 is believed to act as an EDHF physiologically. Thus, there must be competition between the influence of ROS and oxidative stress on NO-dependent dilation versus EDHF-dependent dilation. The crossover effects of ROS on the three main endothelium-dependent dilatory pathways must be examined in hypertension models. Show more

Citation: Clinical Hemorheology and Microcirculation, vol. 37, no. 1-2, pp. 185-192, 2007