Nucleoporin93: Key Guardian of Vascular Health

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"Research in the last several decades has established endothelial cells (ECs) as a dynamic interface critical for vascular protection."

BUFFALO, NY- November 26, 2024 – This editorial was published by Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) in Volume 16, Issue 17 , titled, " The silent protector: Nucleoporin93's role in vascular health ."

Written by Julia Michalkiewicz, Tung D. Nguyen, and Monica Y. Lee from The University of Illinois at Chicago College of Medicine , this editorial highlights the critical role of a protein called Nucleoporin93 (Nup93) in maintaining blood vessel health as we age. The authors review new research suggesting that Nup93 could be a key target for treatments to prevent or reduce aging-related diseases, including heart disease and stroke.

Cardiovascular diseases remain the leading causes of death worldwide, with aging identified as a major risk factor. Vascular health declines as endothelial cells (EC)—the protective lining of blood vessels—lose their functionality with age. This deterioration leads to inflammation, arterial stiffening, and reduced blood flow, significantly increasing the risk of life-threatening diseases. The authors underscore the urgent need to uncover the molecular mechanisms driving these changes.

Nup93 plays an essential role within nuclear pore complexes (NPCs)—gateways that regulate molecular exchanges between the cell nucleus and cytoplasm. Age-related loss of Nup93 disrupts this delicate system, weakening endothelial cells function and accelerating vascular aging. Researchers identified Nup93 as a crucial protector of endothelial health, preventing harmful protein build-ups such as Yes-associated protein (Yap), a known driver of inflammation and cellular aging.

Excitingly, scientists have discovered that restoring Nup93 levels in damaged endothelial cells can reverse some of these harmful effects. They also found that blocking Yap can prevent issues caused by low Nup93 levels. These findings highlight the potential for new medicines or therapies to protect blood vessels as people age.

The authors propose that future treatments could involve delivering Nup93 directly to damaged blood vessels to restore their health and prevent cardiovascular diseases. They emphasize the importance of further research to uncover why Nup93 levels decrease with age and how restoring it might improve blood vessel function.

"These latest discoveries provide a fresh and innovative perspective of EC biology, highlighting NPCs as major regulators of EC health that may underlie mechanisms of vascular aging and disease progression."

In conclusion, the editorial encourages scientists to focus on understanding how endothelial cells stay strong and the role of NPCs in keeping blood vessels healthy. This research could lead to important breakthroughs in slowing down aging and improving people's quality of life.

Read the full paper: DOI: https://doi.org/10.18632/aging.206097

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