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Over-expression of Human SIRT1 Prevents Ageing-induced Endothelial Dysfunction: ENOS Dependent and Independent Mechanisms

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Over-expression of Human SIRT1 Prevents Ageing-induced Endothelial Dysfunction: ENOS Dependent and Independent Mechanisms

4.85 88,919 ratings · 6,682 reviews
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Overview: This dissertation, "Over-expression of Human SIRT1 Prevents Ageing-induced Endothelial Dysfunction: ENOS Dependent and Independent Mechanisms" by Jie, Li, 李杰, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: In blood vessel of mature animal, endothelial cells remain quiescent for years, before apoptosis and being replaced by newly generated endothelial cells. During aging, this turnover process is accelerated and the fast generated endothelial cells become dysfunctional. Endothelial dysfunction in blood vessel is characterized by the imbalanced production of endothelium-dependent relaxing factors (EDRF) and endothelium-dependent contracting factors (EDCF). The NAD-dependent deacetylase SIRT1 is an anti-aging protein with therapeutic potential for aging related cardiovascular diseases. Endothelium-specific over-expression of human SIRT1 promotes endothelium-dependent vasodilatation and endothelium-selective inhibition of human SIRT1 inhibit it. It is accepted that SIRT1 plays a protective role in endothelium dysfunction. However, the underlying mechanisms remain unclear. In the present study, the endothelial functions of a transgenic mouse model with endothelium-selective over-expression of human SIRT1 (hSIRT1) were evaluated and compared with those of wild type mice. Aging-induced deterioration in endothelium-dependent vasodilatation was observed in wild type but not hSIRT1 mice. Endothelium-specific over-expression of SIRT1 prevented aging-induced reduction of NO bioavailability in aortae, without changing endothelial nitric oxide synthase (eNOS) expression levels. Enhanced phosphorylation of eNOS at serine 1177 was detected in hSIRT1 mice aorta. In the presence of Nω-Nitro-L-arginine methyl ester (L-NAME), the nitric oxide synthase (NOS) inhibitor, EDCF induced contraction to acetylcholine was significantly decreased in carotid arteries of hSIRT1 mice. Cyclooxygenase-2 (COX-2) expression was induced by aging in wild-type mice but not in hSIRT1 mice. Thus, both the augmented NO bioavailability and the reduced production of COX-2-derived EDCF in hSIRT1 mice enhanced their endothelial function. To further explore the eNOS-independent mechanism underlying the vasoprotective role of SIRT1, the eNOS deficient and hSIRT1 endothelium-specific over-expression (eNOS-hSIRT1) mice was generated. Decreased endothelium-dependent contraction to acetylcholine was observed in both the carotid artery and aorta of eNOS-hSIRT1 mice, when compared to the controlled eNOS deficient mice. Besides, ATP induced endothelium-dependent contraction, which was COX-dependent, was also decreased in aortae of eNOS-hSIRT1 mice. Thus, the improved endothelial function induced by the endothelium-selective overexpression of SIRT1 was partly attributed to the reduced COX function, independent of eNOS signaling pathway.In summary, endothelium-selective overexpression of human SIRT1 prevented aging-induced impairment of endothelial function via both eNOS dependent and independent mechanisms. DOI: 10.5353/th_b5194769 Subjects: Vascular endothelium - AgingSirtuins

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Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li
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After spending years working in the corporate world, Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li finally decided to pursue a lifelong passion for writing. They currently reside in a quiet suburb where they spend most of their time outlining new stories, reading extensively, and occasionally attempting to bake.

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Exceeded all my expectations. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. An effortless 5 stars.
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Excellent, though slightly flawed. The middle had a deliberate pace, but the climax was phenomenal. Quite impressive overall.
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Such a rich narrative. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I will undoubtedly revisit this masterpiece.
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Excellent, though slightly flawed. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
Eric Young
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Honestly one of the most premium reading experiences lately. I became deeply invested in the protagonist's journey. A masterclass in storytelling. Worth every moment spent reading.
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Honestly one of the most premium reading experiences lately. The prose is exquisite. It’s accessible yet undeniably sophisticated. An effortless 5 stars.
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A very strong entry. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A wonderful companion for a quiet weekend.
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I was completely blown away. The prose is exquisite. It’s accessible yet undeniably sophisticated. An absolute must-read for connoisseurs of the genre.
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Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
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Excellent, though slightly flawed. The middle had a deliberate pace, but the climax was phenomenal. I would highly recommend this to discerning readers.
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I was completely blown away. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
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Such a rich narrative. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I am now a lifelong fan of this author.
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A highly sophisticated read. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
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Absolutely brilliant. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
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Honestly one of the most premium reading experiences lately. The prose is exquisite. It’s accessible yet undeniably sophisticated. A true literary gem.
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A profoundly satisfying read. I adored how the story unfolded. It kept me captivated without sacrificing elegance. I am now a lifelong fan of this author.
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Not entirely to my refined tastes. It possessed moments of brilliance, but the narrative felt slightly disjointed ultimately. Perhaps more aligned with a different audience's tastes.
Donna Hall
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An acceptable diversion. The tempo was somewhat languid, and I found my mind wandering. Not poor, simply average. Perhaps more aligned with a different audience's tastes.
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I find myself somewhat conflicted. The prose was competent, yet the characters lacked the depth I usually seek. Suitable if your reading queue is empty.
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Masterpiece from start to finish. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
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A highly sophisticated read. It held my rapt attention, even when certain twists were telegraphed. A wonderful companion for a quiet weekend.
Rebecca Perez
Rebecca Perez November 26, 2025
Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Thomas Brown
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Absolutely brilliant. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
Christopher Mitchell
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A highly sophisticated read. A brilliant concept executed with flair. Just a few pacing choices I would change. I would highly recommend this to discerning readers.
Charles Cruz
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Excellent, though slightly flawed. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A solid 4 stars from me.
Patricia Johnson
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Took a moment to build, but the payoff was spectacular. The protagonist was compelling, though some subplots felt slightly overshadowed. A very distinguished novel.
John Garcia
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Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. An absolute must-read for connoisseurs of the genre.
Charles Martinez
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Honestly one of the most premium reading experiences lately. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. An effortless 5 stars.
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Such a rich narrative. The prose is exquisite. It’s accessible yet undeniably sophisticated. I am now a lifelong fan of this author.
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Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. An effortless 5 stars.
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A highly sophisticated read. A brilliant concept executed with flair. Just a few pacing choices I would change. A very distinguished novel.
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Honestly one of the most premium reading experiences lately. I adored how the story unfolded. It kept me captivated without sacrificing elegance. An effortless 5 stars.
Donald King
Donald King October 19, 2024
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. An effortless 5 stars.
Donald Clark
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Absolutely brilliant. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
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Excellent, though slightly flawed. The middle had a deliberate pace, but the climax was phenomenal. A very distinguished novel.
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Honestly one of the most premium reading experiences lately. The prose is exquisite. It’s accessible yet undeniably sophisticated. An absolute must-read for connoisseurs of the genre.
Deborah Clark
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A profoundly satisfying read. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
John Jackson
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Honestly one of the most premium reading experiences lately. I became deeply invested in the protagonist's journey. A masterclass in storytelling. Worth every moment spent reading.
Betty  Davis
Betty Davis December 28, 2025
Such a rich narrative. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
Robert Lee
Robert Lee November 07, 2024
I was completely blown away. The prose is exquisite. It’s accessible yet undeniably sophisticated. An absolute must-read for connoisseurs of the genre.
Christopher Sanchez
Christopher Sanchez March 12, 2025
A profoundly satisfying read. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I am now a lifelong fan of this author.
Jacob Collins
Jacob Collins May 07, 2025
Absolutely brilliant. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. An absolute must-read for connoisseurs of the genre.
Betty  Davis
Betty Davis December 19, 2025
A profoundly satisfying read. The prose is exquisite. It’s accessible yet undeniably sophisticated. A true literary gem.
John Torres
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I was completely blown away. The prose is exquisite. It’s accessible yet undeniably sophisticated. Worth every moment spent reading.
Jessica Robinson
Jessica Robinson October 07, 2025
I was completely blown away. The author orchestrated a breathtaking finale. Truly a work of art. I am now a lifelong fan of this author.
Jennifer Allen
Jennifer Allen April 22, 2024
I thoroughly enjoyed the elegance of it. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. I would highly recommend this to discerning readers.
Cynthia Thomas
Cynthia Thomas January 19, 2024
Such a rich narrative. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Sharon Reyes
Sharon Reyes June 11, 2025
Exceeded all my expectations. I adored how the story unfolded. It kept me captivated without sacrificing elegance. A true literary gem.
Barbara Moore
Barbara Moore November 21, 2024
Took a moment to build, but the payoff was spectacular. The middle had a deliberate pace, but the climax was phenomenal. Quite impressive overall.
Stephanie  Parker
Stephanie Parker June 01, 2024
Exceeded all my expectations. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An effortless 5 stars.
Jessica Scott
Jessica Scott February 01, 2024
A profoundly satisfying read. The author orchestrated a breathtaking finale. Truly a work of art. An effortless 5 stars.
Kevin Allen
Kevin Allen December 20, 2025
Honestly one of the most premium reading experiences lately. I adored how the story unfolded. It kept me captivated without sacrificing elegance. Worth every moment spent reading.
John Edwards
John Edwards February 01, 2025
I thoroughly enjoyed the elegance of it. It held my rapt attention, even when certain twists were telegraphed. A very distinguished novel.
Laura Turner
Laura Turner April 05, 2024
Honestly one of the most premium reading experiences lately. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. Worth every moment spent reading.
Mark Adams
Mark Adams September 05, 2025
I thoroughly enjoyed the elegance of it. A brilliant concept executed with flair. Just a few pacing choices I would change. A very distinguished novel.
Daniel Flores
Daniel Flores June 15, 2024
Exceeded all my expectations. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I will undoubtedly revisit this masterpiece.
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