Matrix metalloproteinase imaging and survival prospects with aging in murine aortic aneurysm.
6 affiliations
- 1Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, 300 George Street, Room 770G, New Haven, 06511, CT, USA.
- 2Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA.
- 3Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
- 4Department of Radiology, Washington University, St. Louis, MO, USA.
- 5Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, 300 George Street, Room 770G, New Haven, 06511, CT, USA. [email protected].
- 6Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA. [email protected].
Abstract
Background
Matrix metalloproteinases (MMPs) are elevated in aortic aneurysm (AA), where older age is a risk factor. The relationship among aging, aortic MMP activity, and AA development has not been systematically evaluated. This study leveraged MMP-targeted molecular imaging to investigate how aging affects aortic MMP activity, aneurysm development, and survival.Results
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) apolipoprotein E (Apoe)-/- mice. Old animals' survival at 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 in those that did (P < 0.01). MMP activity significantly increased after Ang-II infusion and correlated with aortic macrophage infiltration. The increase in MMP activity preceded aortic dissection. Finally, MMP activity was heterogeneous along the aorta of control and Ang-II-infused young and old Apoe-/- mice, and of old wild-type mice.Conclusions
Aging is associated with increased MMP activity along the aorta and worse AA survival. MMP-targeted molecular imaging provides insights regarding aneurysm survival prospects in this exploratory cohort. Combining MMP inhibitors and tracers may help prevent and track aneurysm growth, dissection, and rupture.
Related
- Matrix Metalloproteinase Response to Acute Resistance Exercise is Altered in Osteoarthritic Adults with Increased Muscle Collagen and PDGFRα+ Mesenchymal Cells
- Investigation of Matrix Metalloproteinase–Related Genetic Variations Associated With Cavity Formation in Pulmonary Tuberculosis
- Clinical Significance of Tear Matrix Metalloproteinase-9 Reaction Intensity in Thyroid Eye Disease
- Reduction in Rheumatoid Factor and Matrix Metalloproteinase-3 With Successful Glucocorticoid Withdrawal After Initiation of Pemafibrate in a Patient With Rheumatoid Arthritis and Hypertriglyceridemia: A Case Report.
- CO076 | ASSOCIATION OF MATRIX METALLOPROTEINASE 2 PLASMA LEVELS WITH CARDIOVASCULAR EVENTS IN PATIENTS WITH ATRIAL FIBRILLATION: A NESTED CASE CONTROL STUDY FROM THE ATHERO-AF COHORT
BibTeX
@article{ghim2026matrix,
title = {{Matrix metalloproteinase imaging and survival prospects with aging in murine aortic aneurysm.}},
author = {Mean Ghim and Onur Varli and Azmi A Ahmad and Afarin Neishabouri and Gunjan Kukreja and Zhengxing Zhang and Saalar Zarnegar and Nicholas Gangemi and Keshvad Hedayatyanfard and Jakub Toczek and Lingyun Wang and Jiasheng Zhang and Chi Liu and Yongjian Liu and Robert J Gropler and Mehran M Sadeghi},
journal = {EJNMMI research},
year = {2026},
month = sep,
doi = {10.1186/s13550-026-01521-w},
url = {https://europepmc.org/article/MED/42888271},
note = {CC BY},
}
RIS
TY - JOUR
TI - Matrix metalloproteinase imaging and survival prospects with aging in murine aortic aneurysm.
AU - Mean Ghim
AU - Onur Varli
AU - Azmi A Ahmad
AU - Afarin Neishabouri
AU - Gunjan Kukreja
AU - Zhengxing Zhang
AU - Saalar Zarnegar
AU - Nicholas Gangemi
AU - Keshvad Hedayatyanfard
AU - Jakub Toczek
AU - Lingyun Wang
AU - Jiasheng Zhang
AU - Chi Liu
AU - Yongjian Liu
AU - Robert J Gropler
AU - Mehran M Sadeghi
PY - 2026
DA - 2026/09/22
JO - EJNMMI research
DO - 10.1186/s13550-026-01521-w
UR - https://europepmc.org/article/MED/42888271
AB - Background Matrix metalloproteinases (MMPs) are elevated in aortic aneurysm (AA), where older age is a risk factor. The relationship among aging, aortic MMP activity, and AA development has not been systematically evaluated. This study leveraged MMP-targeted molecular imaging to investigate how aging affects aortic MMP activity, aneurysm development, and survival.Results 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) apolipoprotein E (Apoe)-/- mice. Old animals' survival at 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 in those that did (P < 0.01). MMP activity significantly increased after Ang-II infusion and correlated with aortic macrophage infiltration. The increase in MMP activity preceded aortic dissection. Finally, MMP activity was heterogeneous along the aorta of control and Ang-II-infused young and old Apoe-/- mice, and of old wild-type mice.Conclusions Aging is associated with increased MMP activity along the aorta and worse AA survival. MMP-targeted molecular imaging provides insights regarding aneurysm survival prospects in this exploratory cohort. Combining MMP inhibitors and tracers may help prevent and track aneurysm growth, dissection, and rupture.
SN - 2191-219X
ER -