Biomedical subjects

Offer Galili

Publications and source records attributed to Offer Galili.

9 recordsLinked to original sources

PubMed2007

Impaired myocardial perfusion reserve in experimental hypercholesterolemia is independent of myocardial neovascularization.

Our objective was to investigate the functional role of hypercholesterolemia-associated myocardial neovascularization in early atherosclerosis using the antiangiogenic thalidomide. Experimental atherosclerosis is characterized by myocardial neovascularization, associated with a decrease in myocardial perfusion response to challenge, coronary endothelial dysfunction, and high oxidative stress. However, the functional significance of these neovessels is not known. Three groups of pigs (n = 6 each) were studied after 12 wk of normal or hypercholesterolemic diet without (HC) or with thalidomide (HC + Thal). Myocardial perfusion and permeability were assessed at baseline and in response to cardiac challenge, using electron beam computed tomography, and coronary endothelial function was assessed using organ chambers. Myocardial samples were scanned ex vivo with a three-dimensional microscopic computed tomography scanner, and the spatial density of the myocardial microvessels was quantified. Growth factors and oxidative stress were measured in the myocardial tissue. As a results of these procedures, myocardial perfusion response to adenosine and dobutamine was blunted in both HC and HC + Thal pigs compared with normal pigs (P < 0.05, HC and HC + Thal vs. normal) as was the coronary endothelial function. Myocardial permeability response to adenosine was increased in both HC and HC + Thal pigs compared with normal pigs (P < 0.05, HC and HC + Thal vs. normal, and HC + Thal vs. HC). The microvascular density was increased in HC pigs compared with normal pigs but normalized in HC + Thal pigs (P < 0.001 HC vs. normal and HC + Thal). HC + Thal pigs showed decreased expression of Flk-1 and basic FGF but increased expression of VEGF compared with normal and HC pigs. Oxidative stress was increased in both HC and HC + Thal pigs compared with normal pigs. In conclusion, chronic administration of thalidomide attenuates myocardial neovascularization in experimental HC pigs without affecting myocardial perfusion response to stimulation. This suggests that the myocardial neovascularization may not contribute to the attenuated myocardial perfusion response in hypercholesterolemia.

Animals↗

PubMed2006

Placenta growth factor expression in human atherosclerotic carotid plaques is related to plaque destabilization.

BACKGROUND AND PURPOSE: Placenta growth factor (PlGF) mediates angiogenesis and inflammation, but its role in human atherosclerosis is unknown. This study was designed to test the hypothesis that PlGF-expression in human atherosclerotic carotid plaques is related to inflammation, vascularization and clinical plaque instability. METHODS: The expression of PlGF, C-reactive protein (CRP) and CD40L was analyzed with Western blots in carotid plaques of 60 patients. Cellular infiltration (CD68, CD3) and vascularization (von-Willebrand-factor) was assessed by immunohistochemistry. RESULTS: Symptomatic patients showed higher levels of PlGF than asymptomatic patients (115.4+/-8.2 versus 83.6+/-10.5 densitometric units (DU), p<0.05) and higher grading for inflammatory cells and microvessels (CD3: 2.3+/-0.1 versus 0.6+/-0.1, p<0.001, CD68: 2.4+/-0.1 versus 0.8+/-0.1, p<0.001, microvessels: 2.3+/-0.1 versus 1.5+/-0.1, p<0.01). PlGF-expression showed a positive correlation to the expression of CRP (r=0.5, p<0.001) and CD40L (r=0.4, p<0.01). CONCLUSIONS: PlGF-expression within human atherosclerotic lesions is associated with plaque inflammation and microvascular density, suggesting a role for PlGF in plaque destabilization and, thus, in clinical manifestation of the disease.

Aged↗

PubMed2006

Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress.

Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.

Animals↗

PubMed2006

Chronic antioxidant supplementation impairs coronary endothelial function and myocardial perfusion in normal pigs.

Experimental studies have shown the beneficial effects of antioxidant supplementation on endothelial function in the presence of increased endogenous oxidative stress, whereas limited data are available under normal conditions. The present study tested the hypothesis that in normal pigs long-term antioxidants would have deleterious effects on the cardiovascular system. Normal domestic pigs (V, n=6) were studied 12 weeks after dietary supplementation with vitamin E (100 IU/kg per day) and vitamin C (1 g/day) and compared with normal controls (C, n=7). Myocardial perfusion and permeability index were evaluated by electron beam computed tomography after intravenous adenosine and dobutamine. Coronary endothelial function was evaluated in vitro by organ chamber and coronary tissue studied by immunoblotting and staining. Myocardial perfusion response was lower in V than in C after adenosine (10.1+/-4.5 versus 53.4+/-5.2%; P<0.01) and dobutamine (V, 78.4+/-8.1; C, 193.0+/-39.0%; P<0.05). The permeability index increased in V after adenosine (48.8+/-5.1%) and dobutamine (59.9+/-13.6%) and did not change in C. Coronary vasodilation to bradykinin and substance P was lower in V than in C. Moreover, in V, coronary nitrotyrosine and superoxide content was significantly higher than in C. The groups had similar total monomer expression of endothelial nitric oxide synthase, whereas the dimerized form, reflecting coupled enzyme, was lower in V. These findings suggest that long-term experimental antioxidant vitamin supplementation in normal pigs impairs myocardial perfusion and coronary endothelial function via an increased level of oxidative stress in the arterial wall, which may be partly related to the uncoupling of endothelial nitric oxide synthase and/or the direct prooxidant effect of vitamin radicals.

Animals↗

PubMed2005

Dietary reversal of experimental hypercholesterolemia improves endothelial dysfunction of epicardial arteries but not of small coronary vessels in pigs.

Endothelial dysfunction is characterized by impaired vasodilation, increase of oxidative stress and inflammation. The current study was designed to test the hypothesis that reversal of hypercholesterolemic diet alone does not normalize all the parameters of endothelial dysfunction. After 10 weeks on a high-cholesterol diet, female juvenile pigs were randomized to normal diet (n=5, "Reversals") or continued on the same diet (n=6, "HC") for another 6 weeks. A control group of 11 pigs received a normal diet ("C"). Coronary epicardial and arteriolar endothelial function was tested in vitro. NFkappaB and p47phox expression was analyzed in epicardial arteries and myocardium, respectively. P47phox localization in coronary arteries was demonstrated with immunohistochemistry. Lipid levels normalized in Reversal pigs. Epicardial arteries of Reversals showed a normalized relaxation and NFkappaB expression compared to HC (p<0.05). Small vessel relaxation remained attenuated, and expression of p47phox in myocardial tissue was elevated in Reversals compared to C (p<0.05). Dietary lowering of serum cholesterol and LDL improves vascular function of epicardial arteries but neither of small vessels nor vascular oxidative stress within this time frame. Hence, dietary normalization of serum lipid levels alone may not be synonymous to normalization of the components of endothelial dysfunction.

Analysis of Variance↗

PubMed2005

Type IV sacrococcygeal teratoma causing urinary retention: a rare presentation.

Sacrococcygeal teratoma is a rare fetal neoplasm usually diagnosed antenatally and considered benign with no functional impairment. Nevertheless, fetuses with this malformation are at risk of significant perinatal morbidity and mortality, usually implying a malignant component. Management is primarily surgical, with a generally good prognosis. Herein, the authors present a rare and unusual presentation of a type IV sacrococcygeal teratoma as urinary retention in a 7-day-old infant. The diagnostic workup and subsequent surgical treatment are described. The nature of the tumor and the treatment is discussed, emphasizing the need for urgent surgical treatment because of bilateral hydronephrosis that failed to resolve after inserting a urinary catheter.

Female↗

PubMed2005

Experimental hypercholesterolemia differentially affects adventitial vasa vasorum and vessel structure of the left internal thoracic and coronary arteries.

OBJECTIVE: Atherosclerosis is a chronic and diffuse disease that affects all vascular beds. However, some vascular beds are more prone to atherosclerosis than others. Recent evidence suggests a role for the vasa vasorum in the atherosclerotic process. We hypothesized that there is a difference in adventitial vasa vasorum structure between the left internal thoracic artery and the coronary artery. Hence the current study was designed to characterize and compare the structure of the adventitial vasa vasorum in the left internal thoracic and coronary arteries. METHODS: Samples of vessels were obtained from female crossbred domestic pigs maintained on a normal (n = 6) or high-cholesterol (n = 6) diet for 12 weeks. The samples were scanned with micro-computed tomography, and the tomographic images were reconstructed and analyzed to obtain lumen area, vessel wall area, vasa vasorum count, vasa vasorum density, mean diameter of first- and second-order vasa vasorum, and second-order/first-order vasa vasorum ratio. RESULTS: Vasa vasorum density was significantly higher in the coronary arteries versus that seen in the left internal thoracic arteries in the normal group, as well as in the high-cholesterol group. The higher vasa vasorum density in the high-cholesterol group versus that in the normal group was significant for both vessels, being more pronounced in the left internal thoracic artery. Lumen area and second-order/first-order vasa vasorum ratio were higher in the high-cholesterol group than in the normal group only in the left internal thoracic artery. CONCLUSION: This study demonstrated that low vasa vasorum spatial density and higher lumen area observed in the left internal thoracic artery compared with that seen in the native coronary artery can be the structural background for the low incidence of atherosclerosis in this vessel.

Animals↗

PubMed2004

Concurrent treatment with renin-angiotensin system blockers and acetylsalicylic acid reduces nuclear factor kappaB activation and C-reactive protein expression in human carotid artery plaques.

BACKGROUND AND PURPOSE: The local renin-angiotensin system (RAS) and cyclooxygenase-2 contribute to the activation of nuclear factor kappaB (NFkappaB) and C-reactive protein (CRP). We hypothesized that the combination of RAS blockers (RASb) and ASA reduces NFkappaB and CRP within atherosclerotic plaques. METHODS: Patients undergoing carotid endarterectomy were divided into groups according to treatment (RASb-acetylsalicylic acid [ASA], ASA, RASb, and control). The expression of NFkappaB, CRP, and CD40L was analyzed through Western blots in the obtained plaques. RESULTS: Plaques from patients treated with the combination of RASb and ASA showed lower expression of NFkappaB (25.4+/-9.8 densitometric units [DU]) than those of the control group (57.6+/-13.2 DU, P=0.03) as well as lower expression of CRP (20.9+/-9.6 DU) than those of the other treatment groups (ASA 86.1+/-13 DU, RASb 88.4+/-31 DU, controls 67.8+/-18.6, P=0.004). A negative expression of NFkappaB was associated with a reduced incidence of symptoms compared with a positive expression (5/33 [15.1%] versus 14/35 [40%], P=0.031). CONCLUSIONS: The combined treatment with RASb and ASA decreases the expression of inflammatory markers in atherosclerosis in humans. This study supports the role of the local RAS and cyclooxygenase-2 in the progression of atherosclerosis.

Aged↗

PubMed2004

Adventitial vasa vasorum heterogeneity among different vascular beds.

INTRODUCTION: Different vascular beds show substantial variation in their susceptibilities for development of vascular disease like atherosclerosis, and thereby exhibit a variety of different clinical presentations. Yet, the underlying mechanism of this heterogeneity is not well defined. Recent evidence suggests a role for the vasa vasorum (VV) in vascular disease. We hypothesized that there is a differential distribution structure of adventitial VV in different vascular beds. Hence, the current study was designed to characterize and compare the structure of the adventitial VV in the coronary and the peripheral circulation. METHODS: Samples of vessels from different vascular beds were obtained from 6 female crossbred domestic pigs. The samples were scanned using micro-computed tomography, and the images reconstructed and analyzed to characterize VV architecture, including vessel wall area, VV count, VV density, intravessel spatial distribution, mean diameter of first- and second-order VVs and the ratio of second- to first-order VVs. RESULTS: There were significant differences in VV density among different vascular beds. Density was highest in coronary arteries (2.91 +/- 0.26 vessels/mm2, P <.05, vs renal, carotid, and femoral arteries), intermediate in renal arteries (1.45+/- 0.22 vessels/mm2, P <.05, vs femoral artery) and carotid arteries (0.64 +/- 0.08 vessels/mm2, P <.05, vs femoral artery), and lowest in femoral arteries (0.23 +/- 0.05 vessels/mm2 ). A similar pattern for the ratio of second- to first-order VV was also observed. Random intravessel spatial distribution of VVs was seen in all vascular beds. CONCLUSION: The current study demonstrates a differential structure of the adventitial VV in different vascular beds. This intra- and intervessel heterogeneity in VV anatomy is a phenotypic variability that might determine a differential local response to systemic risk factors and, thereby, variable propensity for vascular disease among different vascular beds.

Animals↗