Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility

Abstract

Objective Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. Methods Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. Results Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. Conclusions These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA.

Association between Atrial Fibrillation and Aortic Aneurysms: A Population-Based Cohort Study

“…Degradation of the collagen and elastin of the aortic wall is induced by alteration of the expression of several catabolic MMPs [26]. Patients with AAs showed significantly higher MMP expression levels in their aortic tissue than patients without AAs [27, 28]. Elevated MMP-2, longer AF duration, and atrial extracellular matrix remodeling of AF further increased the risk of difficulties in restoring sinus rhythm in AF patients [29-31].…”

The Role of a Selective P2Y6 Receptor Antagonist, MRS2578, on the Formation of Angiotensin II-Induced Abdominal Aortic Aneurysms

“…Gelatin zymography was performed to evaluate MMP-2 and MMP-9 enzymatic activities in aortic tissues as previously described [23]. Briefly, an equal concentration of extracted protein from mouse aortas was separated on 8% acrylamide-SDS gel containing 1 mg/ml of gelatin at room temperature.…”

Obstructive Sleep Apnoea and Aortic Aneurysm: A Nationwide Population-Based Retrospective Study

“…Plasma MMP-9 levels were found to be high in patients with OSA [34]. Similarly, patients with AA showed significantly higher MMP expression levels in their aortic tissue than patients without AA [35,36]. Several mechanisms, such as induced oxygen free-radical production, activated inflammatory pathways, and impaired endothelial function of vessels, possibly link OSA to AA [37][38][39][40][41].…”