Matrix metalloproteinase imaging and survival prospects with aging in murine aortic aneurysm

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.