Effect of low-density lipoproteins on nitric oxide release, ℓ-arginine uptake, and ℓ-arginine metabolism in cultured endothelial cells : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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College Station, Tex. :
Texas A&M University System Health Science Center,
2001.
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| Subjects: |
| Abstract: | Numerous studies have shown that the vasular dysfunction associated with hypercholesterolemia or atherosclerosis is related to a deficiency of nitric oxide (NO) production from the endothelium. We investigated the effects of native (n-) and oxidized (ox-) low-density lipoprotiens (LDL) on NO release by bovine venular endothelial cells. We ovserved a 30% decrease in A23187-stimulated NO relase by endothelial cells incubated with 0.5 mg protein/ml ox-LDL but not with n-LDL. Since the endothelial dysfunction in atherosclerosis can be restored by exogenous administration of the L-arginine (L-Arg), the precursor to NO, an impairment of L-Arg transport into the endothelium may be one of the factors contributing to the NO deficiency. However, we have found that L-Arg transport was not affected by incubation with LDL. Furthermore, the L-Arg content increased in cells incubated with n- or ox-LDL. Moreover, tetrahydrobiopterin (BH₄) is alos able to reverse the impairment in endothelium-dependent, NO-mediated vasodilation in hypercholesterolemia possibly by replenishing BH₄. However, no significant difference in the intracellular BH₄ in endothelial cells incubated with and without ox-LDL was measurable. The effect of n- or ox-LDL on ecNOS expression and activity was determined using western blotting and enzymatic assay. While the western blots indicated that both n- and ox-LDL decrease ecNOS expression, a decrease in ecNOS activity was only seen for ox-LDL. These studies indicated that the ox-LDL-induced attenuation of NO release from the cultured endothelial cells is more likely due to decrease ecNOS activity and function than to decrease intracellular L-Arg or BH₄. To investigate NO synthesis further, a mathematical model of the enzymes of L-Arg metabolism in endothelial cells was developed. The mathematical model suggests that the increased intracellular L-Arg is more likely due to decreased arginase or OAT activity than to decreased ecNOS activity. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2001." Approved as to style and content by: Lih Kuo, James C. Liao, Cynthia J. Meininger, David C. Zawieja, Harris J. Granger. |
| Physical Description: | xiv, 130 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 81-96). |