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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 14,469 ratings · 77,279 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 is a writer and avid reader based in the Pacific Northwest. Before pursuing writing full-time, they spent over a decade working in education. When not working on their next book, Assistant Professor in the Department of East Asian Languages and Civilizations Jie Li can usually be found hiking with their dog or trying out new coffee shops in their neighborhood.

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Joseph Wilson
Joseph Wilson May 15, 2025
Exceeded all my expectations. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Kimberly Phillips
Kimberly Phillips June 04, 2025
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Honestly one of the most premium reading experiences lately. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
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Exceeded all my expectations. 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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Sarah Martin
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Exceeded all my expectations. 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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A highly sophisticated read. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. Quite impressive overall.
Joseph Garcia
Joseph Garcia January 01, 2025
Absolutely brilliant. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
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I thoroughly enjoyed the elegance of it. The protagonist was compelling, though some subplots felt slightly overshadowed. I would highly recommend this to discerning readers.
Donald Edwards
Donald Edwards October 06, 2025
Exceeded all my expectations. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I will undoubtedly revisit this masterpiece.
Susan Collins
Susan Collins January 20, 2025
A very strong entry. The middle had a deliberate pace, but the climax was phenomenal. A solid 4 stars from me.
Kimberly Phillips
Kimberly Phillips March 23, 2025
A very strong entry. The protagonist was compelling, though some subplots felt slightly overshadowed. A very distinguished novel.
Mark Wright
Mark Wright June 06, 2024
I was completely blown away. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Joseph Clark
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Took a moment to build, but the payoff was spectacular. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A very distinguished novel.
Barbara Gomez
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Not entirely to my refined tastes. Certain acts were fascinating, while others felt like a slight endeavor to complete. A fair 3 stars.
Deborah Johnson
Deborah Johnson September 08, 2025
A highly sophisticated read. The protagonist was compelling, though some subplots felt slightly overshadowed. Quite impressive overall.
James White
James White April 22, 2025
Exceeded all my expectations. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. An absolute must-read for connoisseurs of the genre.
Mark  Parker
Mark Parker October 19, 2024
Honestly one of the most premium reading experiences lately. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. I am now a lifelong fan of this author.
Susan Jackson
Susan Jackson June 12, 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.
Charles Wright
Charles Wright June 04, 2025
Excellent, though slightly flawed. A brilliant concept executed with flair. Just a few pacing choices I would change. A very distinguished novel.
Richard Allen
Richard Allen November 04, 2025
Exceeded all my expectations. I became deeply invested in the protagonist's journey. A masterclass in storytelling. I am now a lifelong fan of this author.
Joseph Clark
Joseph Clark February 29, 2024
I thoroughly enjoyed the elegance of it. A brilliant concept executed with flair. Just a few pacing choices I would change. A wonderful companion for a quiet weekend.
Donna Phillips
Donna Phillips April 25, 2025
Such a rich narrative. The prose is exquisite. It’s accessible yet undeniably sophisticated. I will undoubtedly revisit this masterpiece.
Anthony Collins
Anthony Collins October 04, 2025
Such a rich narrative. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. I am now a lifelong fan of this author.
Steven Turner
Steven Turner September 29, 2025
It was adequate. 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.
David  Parker
David Parker September 18, 2024
Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
Donna Martin
Donna Martin July 10, 2025
I thoroughly enjoyed the elegance of it. A brilliant concept executed with flair. Just a few pacing choices I would change. I would highly recommend this to discerning readers.
Richard Perez
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I was completely blown away. The prose is exquisite. It’s accessible yet undeniably sophisticated. A true literary gem.
Eric Taylor
Eric Taylor July 06, 2025
Masterpiece from start to finish. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An effortless 5 stars.
Patricia Brown
Patricia Brown May 31, 2024
Exceeded all my expectations. The author orchestrated a breathtaking finale. Truly a work of art. I am now a lifelong fan of this author.
Patricia Rivera
Patricia Rivera January 24, 2024
Such a rich narrative. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
Michelle White
Michelle White April 07, 2025
Exceeded all my expectations. I adored how the story unfolded. It kept me captivated without sacrificing elegance. An effortless 5 stars.
Eric Baker
Eric Baker May 19, 2024
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.
Andrew Thompson
Andrew Thompson July 07, 2025
A very strong entry. A brilliant concept executed with flair. Just a few pacing choices I would change. A wonderful companion for a quiet weekend.
Gary Hall
Gary Hall July 18, 2024
A highly sophisticated read. The protagonist was compelling, though some subplots felt slightly overshadowed. A very distinguished novel.
Linda Rodriguez
Linda Rodriguez March 26, 2025
A highly sophisticated read. The protagonist was compelling, though some subplots felt slightly overshadowed. I would highly recommend this to discerning readers.
Daniel Wilson
Daniel Wilson March 24, 2025
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. I will undoubtedly revisit this masterpiece.
Joseph Wilson
Joseph Wilson June 06, 2025
A profoundly satisfying read. I adored how the story unfolded. It kept me captivated without sacrificing elegance. An effortless 5 stars.
Carol Lewis
Carol Lewis March 18, 2024
I thoroughly enjoyed the elegance of it. Beautiful writing, though I craved slightly more depth in the lore. Still, undeniably engaging. A wonderful companion for a quiet weekend.
Emily Jones
Emily Jones February 07, 2024
I was completely blown away. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An effortless 5 stars.
Joseph Clark
Joseph Clark June 27, 2025
Honestly one of the most premium reading experiences lately. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. An absolute must-read for connoisseurs of the genre.
Dorothy Gomez
Dorothy Gomez August 28, 2024
A profoundly satisfying read. I became deeply invested in the protagonist's journey. A masterclass in storytelling. Worth every moment spent reading.
Daniel Nguyen
Daniel Nguyen August 21, 2025
Such a rich narrative. I became deeply invested in the protagonist's journey. A masterclass in storytelling. Worth every moment spent reading.
Nancy Smith
Nancy Smith April 28, 2025
Exceeded all my expectations. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An absolute must-read for connoisseurs of the genre.
Dorothy Smith
Dorothy Smith July 11, 2025
I thoroughly enjoyed the elegance of it. A brilliant concept executed with flair. Just a few pacing choices I would change. A solid 4 stars from me.
Thomas Hall
Thomas Hall January 18, 2025
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.
James Martin
James Martin October 08, 2025
Honestly one of the most premium reading experiences lately. I became deeply invested in the protagonist's journey. A masterclass in storytelling. A true literary gem.
Nancy Rivera
Nancy Rivera November 01, 2025
Masterpiece from start to finish. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
Jennifer Campbell
Jennifer Campbell June 02, 2024
Such a rich narrative. The prose is exquisite. It’s accessible yet undeniably sophisticated. Worth every moment spent reading.
Nicholas Ramirez
Nicholas Ramirez July 27, 2025
I thoroughly enjoyed the elegance of it. The middle had a deliberate pace, but the climax was phenomenal. A wonderful companion for a quiet weekend.
George Mitchell
George Mitchell May 05, 2024
I was completely blown away. I adored how the story unfolded. It kept me captivated without sacrificing elegance. I will undoubtedly revisit this masterpiece.
Margaret Gomez
Margaret Gomez August 13, 2024
Masterpiece from start to finish. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. A true literary gem.
Barbara White
Barbara White November 04, 2024
A profoundly satisfying read. I adored how the story unfolded. It kept me captivated without sacrificing elegance. A true literary gem.
Sandra Thomas
Sandra Thomas May 11, 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.
Patricia Green
Patricia Green May 14, 2025
Honestly one of the most premium reading experiences lately. I became deeply invested in the protagonist's journey. A masterclass in storytelling. A true literary gem.
Margaret Rivera
Margaret Rivera July 10, 2024
I thoroughly enjoyed the elegance of it. The protagonist was compelling, though some subplots felt slightly overshadowed. A solid 4 stars from me.
Michael Garcia
Michael Garcia April 27, 2025
An acceptable diversion. 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.
James Young
James Young November 24, 2025
A highly sophisticated read. The protagonist was compelling, though some subplots felt slightly overshadowed. I would highly recommend this to discerning readers.
Susan Ramirez
Susan Ramirez October 05, 2024
Absolutely brilliant. The author orchestrated a breathtaking finale. Truly a work of art. A true literary gem.
Thomas Allen
Thomas Allen February 29, 2024
Absolutely brilliant. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. Worth every moment spent reading.
Kenneth Rivera
Kenneth Rivera September 01, 2024
Absolutely brilliant. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. I will undoubtedly revisit this masterpiece.
Linda Roberts
Linda Roberts November 10, 2025
Masterpiece from start to finish. It strikes a perfect harmony of dialogue and world-building. Every chapter felt necessary. An effortless 5 stars.
Dorothy King
Dorothy King September 01, 2024
I thoroughly enjoyed the elegance of it. The protagonist was compelling, though some subplots felt slightly overshadowed. Quite impressive overall.
Richard Flores
Richard Flores February 12, 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.
Mark Harris
Mark Harris September 30, 2024
Absolutely brilliant. The prose is exquisite. It’s accessible yet undeniably sophisticated. Worth every moment spent reading.
Patricia Lewis
Patricia Lewis March 12, 2024
Took a moment to build, but the payoff was spectacular. It held my rapt attention, even when certain twists were telegraphed. A wonderful companion for a quiet weekend.
Sandra  Davis
Sandra Davis March 17, 2025
Such a rich narrative. I became deeply invested in the protagonist's journey. A masterclass in storytelling. An absolute must-read for connoisseurs of the genre.
Richard Taylor
Richard Taylor August 12, 2024
Honestly one of the most premium reading experiences lately. The pacing was impeccable and the characters felt incredibly authentic. I was completely immersed. A true literary gem.
William Reyes
William Reyes July 15, 2025
Honestly one of the most premium reading experiences lately. The author orchestrated a breathtaking finale. Truly a work of art. An effortless 5 stars.
Brian Thomas
Brian Thomas July 18, 2024
A profoundly satisfying read. The author orchestrated a breathtaking finale. Truly a work of art. Worth every moment spent reading.
James Young
James Young August 08, 2025
An acceptable diversion. It verged on repetitive in the second act. A more concise edit would have served it well. Suitable if your reading queue is empty.
Gary Gonzalez
Gary Gonzalez January 10, 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.
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