Aging, matrix metalloproteinase imaging, and survival prospects in aortic aneurysm

Sep 30, 2026

Uploaded by Kyle

Age increases risk for aortic aneurysm (AA), yet the mechanisms linking aging to higher AA incidence and complications remain insufficiently defined. Matrix metalloproteinases (MMPs) are elevated in AA, but whether aging alters aortic MMP expression and activity to drive AA development and survival has not been systematically assessed. This study used MMP-targeted molecular imaging to test how aging affects aortic MMP biology, aneurysm development, and 28-day survival following Ang-II exposure in Apoe-/- mice.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages31

Reading Time1 h 18 min

AccessFree to download

Abstract

Methods

Results

Conclusion

Keywords

bioRxiv preprint doi: [https://doi.org/10.64898/2026.01.02.697375](https://doi.org/10.64898/2026.01.02.697375); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Aging, matrix metalloproteinase imaging, and survival prospects in aortic aneurysm Mean Ghim, PhD 1 , Onur Varli, MD 1 , Azmi A. Ahmad, PhD 1,2 , Afarin Neishabouri, MD 1,2 , Gunjan Kukreja, PhD 1,2 , Zhengxing Zhang, PhD 1 , Saalar Zarnegar1 , Nicholas Gangemi 1 , Jakub Toczek, PhD 1,2 , PhD, Jiasheng Zhang, MD 1 , Chi Liu, PhD3 , Yongjian Liu, PhD4 , Robert J. Gropler, MD4 , Mehran M. Sadeghi, MD 1,2 1 Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA 2 Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA 3 Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA 4 Department of Radiology, Washington University, St. Louis, MO, USA Corresponding Author: Mehran M. Sadeghi, M. D. Professor of Medicine (Cardiology) Yale School of Medicine 300 George Street, Room 770G New Haven, CT 06511, USA Phone: 203-737 6954 Fax: 203-937 3884 [Email:](Email: mehran.sadeghi@yale.edu)[ ](Email: mehran.sadeghi@yale.edu)[mehran.sadeghi@yale.edu](Email: mehran.sadeghi@yale.edu) [ORCID ID: 0000-0002-5074-3510](ORCID ID: 0000-0002-5074-3510) bioRxiv preprint doi: [https://doi.org/10.64898/2026.01.02.697375](https://doi.org/10.64898/2026.01.02.697375); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Abstract Age is a risk factor for aortic aneurysm (AA), and different segments of the aorta exhibit varying susceptibilities to aneurysm. The specific factors that contribute to the higher incidence of AA and its complications with aging remain unclear. Matrix metalloproteinases (MMPs) are elevated in AA. However, the connection between aging, aortic MMP activity, and the increased prevalence of AA and its complications has not been systematically evaluated. This study leveraged MMP-targeted molecular imaging to investigate how aging affects aortic MMP expression and activity, as well as aneurysm development and survival. Methods: AA development and animal survival were monitored for 28 days after Angiotensin (Ang)-II infusion in 8-10-week-old (young) and >51-week-old (old) Apoe-/- mice. Aortic MMP activation was quantified by PET/CT using an MMP-targeted tracer, 64Cu-RYM2, at baseline and 1 week after Ang II infusion. MMP activity and expression were quantified by tissue zymography and quantitative reverse transcription polymerase chain reaction, and compared between different segments of the aorta in young and old animals, and before and after Ang II infusion. Results: Old animals’ survival to 28 days was significantly lower than that of young Ang-II-infused Apoe-/- mice (P < 0.05) . 64Cu-RYM2 PET/CT showed significantly higher aortic MMP activation before and 1 week after Ang-II infusion in old compared to young Apoe-/-mice. The 64Cu-RYM2 signal was significantly higher in animals that did not survive 28 days than those that did (P < 0.01) . MMP activity significantly increased by 4 days after Ang-II infusion, when dissection was found in a subset of Apoe-/- mice; and was significantly higher in the dissected, compared to adjacent, apparently normal, segments of the aorta. MMP activity was also significantly higher in the ascending thoracic aorta of untreated young and old mice, as well as ofAng-II-treated Apoe-/- mice (which was associated with significantl

FAQs

How was aging modeled and what animal groups were compared?

AA development and animal survival were monitored for 28 days after Ang-II infusion in 8–10-week-old (young) and >51-week-old (old) Apoe-/- mice.

What imaging and assays quantified MMP activation, activity, and expression?

A PET/CT MMP-targeted tracer, 64Cu-RYM2, quantified aortic MMP activation at baseline and 1 week after Ang-II infusion. Tissue zymography and quantitative reverse transcription polymerase chain reaction measured MMP activity and expression.

What main findings linked aging to MMP activity and AA survival?

Old animals showed significantly lower 28-day survival after Ang-II. 64Cu-RYM2 PET/CT indicated higher aortic MMP activation in old versus young animals, and higher signal in animals that did not survive 28 days. MMP activity increased after 4 days, associated with dissection in a subset of mice.

Sep 30, 2026

Uploaded by Kyle