Hemodynamic forces play an active role in vascular pathologies, particularly in relation to the localization of atherosclerotic lesions. It has been established that low shear stress combined with cyclic reversal of flow direction (oscillatory shear stress) affects the endothelial cells and may lead to an initiation of plaque development. The aim of the study was to analyze the effect of hemodynamic conditions in arterial segments perfused in vitro in the absence of other stimuli. Left common porcine carotid segments were mounted into an ex vivo arterial support system and perfused for 3 days under unidirectional high and low shear stress (6 +/- 3 and 0.3 +/- 0.1 dyn/cm(2)) and oscillatory shear stress (0.3 +/- 3 dyn/cm(2)). Bradykinin-induced vasorelaxation was drastically decreased in arteries exposed to oscillatory shear stress compared with unidirectional shear stress. Impaired nitric oxide-mediated vasodilation was correlated to changes in both endothelial nitric oxide synthase (eNOS) gene expression and activation in response to bradykinin treatment. This study determined the flow-mediated effects on native tissue perfused with physiologically relevant flows and supports the hypothesis that oscillatory shear stress is a determinant factor in early stages of atherosclerosis. Indeed, oscillatory shear stress induces an endothelial dysfunction, whereas unidirectional shear stress preserves the function of endothelial cells. Endothelial dysfunction is directly mediated by a downregulation of eNOS gene expression and activation; consequently, a decrease of nitric oxide production and/or bioavailability occurs.
Background: The aim of this study was to analyze the arterial wall response to plaque-prone hemodynamic environments, known to occur mainly in areas of arterial trees such as bifurcations and branching points. In these areas, the vasculature is exposed to cyclically reversing flow that induces an endothelial dysfunction predisposing thus arteries to local development of atherosclerotic plaques. Methods: We used an ex vivo perfusion system that allows culturing arterial segments under different hemodynamic conditions. Porcine carotid arteries were exposed for 3 days to unidirectional high and low shear stress (6 ± 3 and 0.3 ± 0.1 dyn/cm2) as well as to oscillatory shear stress (0.3 ± 3 dyn/cm2). This latter condition mimics the hemodynamics present at plaque-prone areas. At the end of the perfusion, the influence of different flow patterns on arterial metabolism was assessed in terms of matrix turnover as well as of smooth muscle cell function, differentiation and migration. Results: Our results show that after 3 days of perfusion none of the applied conditions influence smooth muscle cell phenotype retaining their full contraction capacity. However, an increase in the expression level of matrix metalloproteinase-2 and -9, as well as a decrease in plasminogen activator inhibitor-1 expression were observed in arteries exposed to oscillatory shear stress when compared to arteries exposed to unidirectional shear stress. Conclusion: These observations suggest that plaque-prone hemodynamic environment triggers a vascular wall remodelling process and promotes changes in arterial wall metabolism, with important implication in atherogenesis.
Summary. Recent reports show a correlation between haemophilia and osteoporosis. HIV, HCV and their treatments are independently associated with an increased risk of osteoporosis. Vitamin D plays a pivotal role in bone mineralization. The aim of our study was to compare Vitamin D levels, bone metabolism markers and bone mineral density (BMD) in patients with haemophilia with or without co-infections. Seventy-eight adult patients with severe or moderate haemophilia A or B were subdivided into three groups of 26 patients each (HIV-HCV co-infected, HCV mono-infected and uninfected). The BMD was measured by dual energy X-ray absorptiometry (DXA) at both the femoral area (F) and lumbar spine (L). This was correlated to laboratory values and haemophilic arthropathy was assessed using validated clinical and radiological scores. The DXA showed a homogeneous F-BMD reduction in all the three groups, whereas L-BMD was significantly lower in co-infected patients (P < 0.05). The clinical score was higher in co-infected (P < 0.002) and mono-infected (P < 0.006). The radiological score was higher in mono-infected than in the other two groups (P < 0.001). Overall 25-hydroxyvitamin D (25-OH Vit D) was reduced (87%). Bone-specific alkaline phosphatase (b-ALP) and telopeptide were increased in co-infected (P < 0.001 and P < 0.01) and mono-infected (P < 0.001 and P < 0.02). The result of the homogeneous F-BMD reduction in all groups could be explained by the pivotal role of arthropathy; the lower L-BMD in co-infected and the increase of b-ALP and telopeptide in co-infected and mono-infected groups suggest faster bone metabolism in case of infections.Keywords: osteoporosis, vitamin D, haemophilic arthropathy, HCV, HIV, HAART IntroductionRecent evidence suggests a strong correlation between osteoporosis and haemophilia. The pathogenesis of low bone mineral density (BMD) in patients with haemophilia is multi-factorial and primarily includes prolonged immobilization [1,2], lack of weight-bearing exercise [3] and an increased bone turnover mediated by pro-inflammatory cytokines and osteoclastogenesis activating factors [4,5]. Other factors such as HIV or HCV infections and their treatment may be independently associated with decreased BMD [1,4]. Osteoporosis is a disorder characterized by both quantitative and qualitative alterations that reduce bone strength [6]. Bone densitometry measured by dual X-ray absorptiometry scan (DXA) is the current gold standard test for assessing bone mineralization [7]. Biomarkers of bone formation and resorption reflecting the activity of osteoblasts and osteoclasts, respectively, have also been developed to increase knowledge on the bone turnover pathophysiology [8].A pivotal and well-established role in bone mineralization is played by vitamin D. In the last years, hypovitaminosis D has been shown to be extremely common and prevalent across all age groups, gender Haemophilia ( 2013 ), 19, 126-133 DOI: 10.1111 /j.1365 -2516 .2012 and geographic areas [9][10][11]. However, little data about the prevalen...
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