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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 26,385 ratings · 8,367 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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Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li
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Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li writes contemporary fiction and has always been fascinated by character-driven stories. They hold a degree in English Literature and previously worked as an editor before transitioning to writing their own books. Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li lives with their spouse and a very vocal rescue cat.

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Barbara Harris
Barbara Harris January 02, 2024
Exceeded all my expectations. 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 pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. A true literary gem.
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A profoundly satisfying read. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An absolute must-read for connoisseurs of the genre.
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Masterpiece from start to finish. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I will undoubtedly revisit this masterpiece.
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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. I will undoubtedly revisit this masterpiece.
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A very strong entry. A brilliant concept executed with flair. Just a few pacing choices I would change. A very distinguished novel.
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Masterpiece from start to finish. 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. A brilliant concept executed with flair. Just a few pacing choices I would change. I would highly recommend this to discerning readers.
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A highly sophisticated read. The middle had a deliberate pace, but the climax was phenomenal. I would highly recommend this to discerning readers.
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Excellent, though slightly flawed. The protagonist was compelling, though some subplots felt slightly overshadowed. I would highly recommend this to discerning readers.
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A profoundly satisfying read. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
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Masterpiece from start to finish. 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.
George Mitchell
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Masterpiece from start to finish. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. An absolute must-read for connoisseurs of the genre.
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I was completely blown away. The prose is exquisite. It’s accessible yet undeniably sophisticated. A true literary gem.
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I thoroughly enjoyed the elegance of it. It held my rapt attention, even when certain twists were telegraphed. A solid 4 stars from me.
Sharon Roberts
Sharon Roberts August 26, 2025
Excellent, though slightly flawed. A brilliant concept executed with flair. Just a few pacing choices I would change. A wonderful companion for a quiet weekend.
Donald Mitchell
Donald Mitchell November 27, 2024
A profoundly satisfying read. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. I will undoubtedly revisit this masterpiece.
Brian Hernandez
Brian Hernandez May 08, 2025
A profoundly satisfying read. The prose is exquisite. It’s accessible yet undeniably sophisticated. An absolute must-read for connoisseurs of the genre.
Kevin Johnson
Kevin Johnson July 09, 2024
A highly sophisticated read. It held my rapt attention, even when certain twists were telegraphed. A solid 4 stars from me.
David Garcia
David Garcia December 20, 2025
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Anthony Adams
Anthony Adams February 26, 2025
Absolutely brilliant. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Christopher Perez
Christopher Perez July 21, 2025
A highly sophisticated read. It held my rapt attention, even when certain twists were telegraphed. A wonderful companion for a quiet weekend.
Sandra Phillips
Sandra Phillips August 12, 2025
Absolutely brilliant. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Sandra Brown
Sandra Brown June 08, 2024
Honestly one of the most premium reading experiences lately. I adored how the story unfolded. It kept me captivated without sacrificing elegance. An absolute must-read for connoisseurs of the genre.
Deborah Brown
Deborah Brown March 12, 2025
Such a rich narrative. The prose is exquisite. It’s accessible yet undeniably sophisticated. I am now a lifelong fan of this author.
Anthony Moore
Anthony Moore September 26, 2025
Took a moment to build, but the payoff was spectacular. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
Donald Perez
Donald Perez September 19, 2024
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Joshua Torres
Joshua Torres July 04, 2025
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
Edward Green
Edward Green December 30, 2024
I was completely blown away. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
Deborah Thomas
Deborah Thomas May 26, 2025
Took a moment to build, but the payoff was spectacular. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. I would highly recommend this to discerning readers.
Eric King
Eric King July 10, 2025
A highly sophisticated read. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A solid 4 stars from me.
Steven Garcia
Steven Garcia October 22, 2025
Masterpiece from start to finish. The prose is exquisite. It’s accessible yet undeniably sophisticated. An effortless 5 stars.
Betty Flores
Betty Flores June 10, 2025
A profoundly satisfying read. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Jessica Martin
Jessica Martin February 14, 2024
I was completely blown away. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I will undoubtedly revisit this masterpiece.
Jessica Jones
Jessica Jones May 22, 2024
A highly sophisticated read. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
Richard Baker
Richard Baker January 13, 2025
Absolutely brilliant. The author orchestrated a breathtaking finale. Truly a work of art. An absolute must-read for connoisseurs of the genre.
Sarah Moore
Sarah Moore November 10, 2024
A decent, if standard, experience. It possessed moments of brilliance, but the narrative felt slightly disjointed ultimately. Perhaps more aligned with a different audience's tastes.
Amanda  Davis
Amanda Davis October 27, 2024
An acceptable diversion. It possessed moments of brilliance, but the narrative felt slightly disjointed ultimately. Unlikely to reread, but a reasonable expenditure of time.
Michael Baker
Michael Baker May 04, 2025
Honestly one of the most premium reading experiences lately. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Kimberly Perez
Kimberly Perez August 15, 2024
A profoundly satisfying read. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Margaret White
Margaret White October 01, 2025
A profoundly satisfying read. The prose is exquisite. It’s accessible yet undeniably sophisticated. A true literary gem.
Melissa Clark
Melissa Clark October 14, 2024
A decent, if standard, experience. The prose was competent, yet the characters lacked the depth I usually seek. Suitable if your reading queue is empty.
Carol Nelson
Carol Nelson December 05, 2025
Masterpiece from start to finish. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. A true literary gem.
Kevin Mitchell
Kevin Mitchell June 17, 2024
Masterpiece from start to finish. The prose is exquisite. It’s accessible yet undeniably sophisticated. An absolute must-read for connoisseurs of the genre.
Matthew Young
Matthew Young February 02, 2025
I thoroughly enjoyed the elegance of it. The protagonist was compelling, though some subplots felt slightly overshadowed. A solid 4 stars from me.
Daniel Campbell
Daniel Campbell August 16, 2024
Took a moment to build, but the payoff was spectacular. A brilliant concept executed with flair. Just a few pacing choices I would change. A solid 4 stars from me.
Michelle Lee
Michelle Lee January 15, 2025
Absolutely brilliant. I adored how the story unfolded. It kept me captivated without sacrificing elegance. A true literary gem.
Laura Harris
Laura Harris October 03, 2025
Honestly one of the most premium reading experiences lately. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. An absolute must-read for connoisseurs of the genre.
Barbara Martinez
Barbara Martinez February 18, 2025
Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
Kevin Scott
Kevin Scott May 04, 2024
Absolutely brilliant. I adored how the story unfolded. It kept me captivated without sacrificing elegance. I am now a lifelong fan of this author.
Mark Walker
Mark Walker March 19, 2024
Took a moment to build, but the payoff was spectacular. It held my rapt attention, even when certain twists were telegraphed. A solid 4 stars from me.
Ryan Cruz
Ryan Cruz April 08, 2024
Excellent, though slightly flawed. The protagonist was compelling, though some subplots felt slightly overshadowed. Quite impressive overall.
Elizabeth Thompson
Elizabeth Thompson December 03, 2024
Exceeded all my expectations. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I am now a lifelong fan of this author.
Sarah Campbell
Sarah Campbell November 05, 2024
Not entirely to my refined tastes. Certain acts were fascinating, while others felt like a slight endeavor to complete. Perhaps more aligned with a different audience's tastes.
Karen Green
Karen Green August 17, 2024
Absolutely brilliant. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. I will undoubtedly revisit this masterpiece.
Kenneth Green
Kenneth Green September 06, 2024
Masterpiece from start to finish. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I will undoubtedly revisit this masterpiece.
Kevin Scott
Kevin Scott January 20, 2024
A profoundly satisfying read. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Brian Collins
Brian Collins September 13, 2025
Honestly one of the most premium reading experiences lately. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. An effortless 5 stars.
Nancy Diaz
Nancy Diaz March 22, 2024
Excellent, though slightly flawed. A brilliant concept executed with flair. Just a few pacing choices I would change. A very distinguished novel.
Steven Sanchez
Steven Sanchez September 30, 2025
Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. An absolute must-read for connoisseurs of the genre.
Christopher King
Christopher King December 08, 2024
Absolutely brilliant. I became deeply invested in the protagonist's journey. A masterclass in storytelling. Worth every moment spent reading.
Mark Jackson
Mark Jackson April 23, 2024
Honestly one of the most premium reading experiences lately. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I will undoubtedly revisit this masterpiece.
George Roberts
George Roberts July 04, 2025
A highly sophisticated read. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A solid 4 stars from me.
Anthony Lewis
Anthony Lewis July 18, 2024
A profoundly satisfying read. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. A true literary gem.
Nancy  Parker
Nancy Parker April 06, 2024
Honestly one of the most premium reading experiences lately. I adored how the story unfolded. It kept me captivated without sacrificing elegance. A true literary gem.
Lisa Allen
Lisa Allen October 03, 2025
An acceptable diversion. Certain acts were fascinating, while others felt like a slight endeavor to complete. Suitable if your reading queue is empty.
Margaret Anderson
Margaret Anderson September 26, 2024
Absolutely brilliant. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
Mary White
Mary White January 29, 2024
I was completely blown away. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
Melissa Clark
Melissa Clark October 05, 2025
Excellent, though slightly flawed. A brilliant concept executed with flair. Just a few pacing choices I would change. Quite impressive overall.
Joshua Wilson
Joshua Wilson August 15, 2024
Masterpiece from start to finish. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Mary Martin
Mary Martin June 23, 2024
Absolutely brilliant. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Amanda Gonzalez
Amanda Gonzalez September 12, 2025
Honestly one of the most premium reading experiences lately. The prose is exquisite. It’s accessible yet undeniably sophisticated. An effortless 5 stars.
David Garcia
David Garcia January 05, 2024
Such a rich narrative. The prose is exquisite. It’s accessible yet undeniably sophisticated. An effortless 5 stars.
Lisa Rodriguez
Lisa Rodriguez July 11, 2024
I was completely blown away. I adored how the story unfolded. It kept me captivated without sacrificing elegance. An absolute must-read for connoisseurs of the genre.
Rebecca Torres
Rebecca Torres February 24, 2025
Masterpiece from start to finish. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. Worth every moment spent reading.
Carol Jackson
Carol Jackson April 06, 2024
Excellent, though slightly flawed. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
Dorothy Williams
Dorothy Williams March 12, 2024
Masterpiece from start to finish. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. I am now a lifelong fan of this author.
Barbara Green
Barbara Green October 12, 2025
A decent, if standard, experience. It verged on repetitive in the second act. A more concise edit would have served it well. Unlikely to reread, but a reasonable expenditure of time.
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