Abdominal aortic aneurysm (AAA) is a pathological condition that affects 2-8% of the population older than 60 years of age. Aneurysm formation and aortic dissection occur as a result of drastic changes to the structure of the aortic wall, occurring due to steady breakdown of the extracellular matrix (ECM) proteins, chronic inflammation and oxidative stress. Matrix metalloproteinases (MMPs) are involved in the degradation of the ECM components which are vital in the maintenance of the integrity of the aortic wall.
The recent study in Circulation Research by Mani Salarian, PhD, and Mean Ghim, PhD, from the Cardiovascular Molecular Imaging Laboratory demonstrates that the MMP-12 is crucial for maintaining vascular homeostasis. Using several transgenic mouse models, the authors show that deficiency of MMP-12 leads to complement activation as well as increased levels of neutrophil extracellular traps (NETs). Subsequently, this mediates a loss of vascular integrity and higher susceptibility to AAA and its rupture. The results of the study also highlight the possibility that genetic and nongenetic factors that regulate MMP-12 expression could predispose to AAA and other vascular pathologies. The findings are clinically significant as they advocate caution in the use of selective MMP-12 inhibitors as therapeutic agents in AAA and other vascular pathologies.