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" The effect of Nitric Oxid donor ( L-arginine ) on the endothelial dysfunction process and recovery: Dose L-arginine Prevent endothelial dysfunction through endothelial cell apoptosis inhibition, alteration of the NOS enzymes expression, or VEGF secretion ? "
/شقایق حقجوی جوانمرد
; Mehdi Nematbakhsh
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Isfahan University of Medical Sciences
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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102670
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| Doc. No
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T10961
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| Call number
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WG,550,H145e,2007
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| Main Entry
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Haghjooyejavanmard, Shaghayegh
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The effect of Nitric Oxid donor ( L-arginine ) on the endothelial dysfunction process and recovery: Dose L-arginine Prevent endothelial dysfunction through endothelial cell apoptosis inhibition, alteration of the NOS enzymes expression, or VEGF secretion ?/شقایق حقجوی جوانمرد
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Schools, Medical
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| Date
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, 2007
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| Degree
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Physiology, Ph.D
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Xiv, 262 p.:Ill( color ), diag, tab
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| Note
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Orginal Works
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| Abstract
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Introduction: Atherosclerosis is the single most important cause of CVD - a predominant health problem worldwide. As atherosclerosis has a long asymptomatic phase and the first manifestation of disease may be sudden cardiac death, it is imperative to find effective strategies to prevent it. Current guidelines for the prevention of atherosclerotic diseases focus on treatment of established cardiovascular risk factors to attenuate the subsequent endothelial cell dysfunction and damage. Endothelial Dysfunction (ED) is an early event in atherosclerosis and has a pivotal role in the atherogenesis process. ED is characterized by reduced bioavailability of nitric oxide (NO). NO is a potent anti-atherosclerotic molecule and every intervention that enhances NO bioavailability might be a promising strategy for the prevention and treatment of atherosclerosis. . L-Arginine is the substrate of endothelial nitric oxide synthase (eNOS) and the main precursor of NO in the vascular endothelium. Although Larginine seems suitable intervention for accelerating endothelial dysfunction recovery there is still no conclusive evidence for its use for primary or secondary prevention of adverse cardiovascular events. This study was designed to investigate some proposed mechanism of anti-atherosclerotic effects of L arginine including augmentation of NO production and improving ED, suppression of inflammatory processes, inhibition of apoptosis, enhancement of the eNOS expression and diminishing the iNOS expression. Method: Forty-eight white male rabbits were randomly assigned in 2 groups. The rabbits were fed rabbit chow supplemented with 1 cholesterol. (Hypercholesterolemic diet) (group 1, n=24) or high-cholesterol diet with oral L-arginine (3 in drinking water) (group 2, n=24) for one month (phase I). During this phase the blood sampling episode was repeated every ten days and the serum level of total cholesterol, LDL, HDL, triglyceride, nitrite, vWF, CRP, VEGF. By the end phase I, the half of the animals of each group randomly were euthanized. The animal's aortas were harvested for pathological investigation. From this point, hypercholesterolemic diet of all groups was break off and all animal were on normal diet, and the experiment was continued for another 30 days (phase II). 12 animals from each groups of previous phase were subjected to begin the second phase. The reminder animals of group 1 were divided in to two subgroups which were called as Positive Control (PC) and Treatment (TREAT) groups. The reminder animals of group 2 were divided in to two subgroups which were called as Prevention (PREV) and Prevention and Treatment (PRE&TREAT) groups. The PC and PREV groups received normal diet and tap water. The TREAT and PRE&TREAT groups received normal diet and 3 L arginine in drinking water. During this phase, the blood sampling episode was also repeated every ten days (E, F, and G episodes of blood sampling). By the end of the phase H, the rest of the animals were scarified and aortas were harvested for pathological investigation. The serum level of total cholesterol, LDL, HDL, triglyceride, nitrite, vWF, CRP, and VEGF were measured. The fatty streaks formation, eNOS, iNOS, 'and number of intimal apoptotic cells were investigated in rabbit's aorta. Results: Hypercholesterolemic diet induced hypercholesterolemia in both groups of first phase. There was no significant difference between two groups. By the end of the first phase, the serum level of nitrite was significantly higher in L arginine treated group. The serum level of vWF was significantly lower in L arginine treated group. The serum level of VEGF was significantly lower in L arginine treated group. There was no significant difference in CRP concentration between two groups of the study. Fatty streaks formation was significantly lower in L-arginine treated group. The eNOS expression in rabbit's aortas was significantly higher in L-arginine treated group (p<0.05). The iNOS expression in rabbit's aortas was lower in L-arginine treated group however the difference was not significant. L- Arginine supplementation led to significant lower intimal apoptotic cells. In second phase, hypercholesterolemic diet withdrawal led to significant decrease of serum cholesterol concentration. L arginine has no effect on this decrement. There were no significant differences in serum levels of nitrite and CRP between groups. Serum levels of vWF were significantly higher in PRE& TREAT group than all other groups. Serum levels of VEGF were significantly higher in PC group than all other groups. There was only significant different fatty streaks formation between PC and PREY group. There were no significant differences in eNOS and iNOS expression, and intimal cell apoptosis between groups. Conclusion: The PC group of the present study provide the opportunity to monitor endothelial state from ED to fatty streaks formation and the impact of early atherosclerosis as a disease state on a package of known biomarkers of ED. Furthermore, hypercholesterolemic diet withdrawal and the consequential risk factor modification serve as a good model to find a suitable marker for investigating the efficacy of therapeutic interventions. VWF is the best biological marker of those tested for identifying risk of developing atherosclerosis. As the results of our study showed, L arginine had the most beneficial effects when used as a preventive agent and its supplementation in both prevention and treatment approach didn't have more beneficial effects. Keywords: Endothelial dysfunction, Atherosclerosis, L-arginine, Nitric Oxide, von Willebrand Factor, Vascular endothelial growth factor, C- Reactive protein.
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| Descriptor
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1.Atherosclerosis.- Descriptors: Atherosclerosis- prevention and control
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Endothelium
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Cardiovascular Disease
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Biological Availability
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Nitric Oxide
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Arginine
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| Added Entry
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Nematbakhsh, Mehdi, Supervisor
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| Translated Title Supplied by Cataloguer
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بررسی مکانیسم و برخی از فاکتورهای موثر بر اختلال عملکرد آندوتلیوم و بازگشت پذیری آن
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