As early as day 3 following Ang II infusion, prior to the development of AD, Lnk-/- aortas display altered mechanical properties, increased elastin breaks, collagen thinning, enhanced neutrophil accumulation, and increased MMP-9 activity compared with WT mice.
In conclusion, mechanical stretch aggravated aortic dissection by regulating the MAPK pathway and the consequent expression of MMP-9 and inflammation factors.
MATERIAL AND METHODS Twenty-four 8-month-old C57BL/6J mice were divided into three groups and studied for two weeks: 1) the aortic dissection (AD) Model group (N=8) underwent intraperitoneal injection of angiotensin II (Ang II) (5 ml/kg) three times every 24 h; 2) the mercaptoethanol Treated group (N=8) were given oral mercaptoethanol (2.5 mM); the Normal group (N=8) underwent intraperitoneal injection of noradrenaline (5 mg/kg) three times every 24 h. Sections of mouse aorta were prepared for histology with hematoxylin and eosin (H&E) staining; immunohistochemistry was performed to detect levels of: nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), nuclear factor κB (NF-κB), p65, superoxide dismutase-1 (SOD1), glutamate cysteine ligase catalytic subunit (GCLC), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and matrix metalloproteinase-9 (MMP9).
The results showed increased expression of MMP-9 in rat AD vessels stretched with mechanical strength of 1 g, 3 g, and 5 g, but this effect was mostly blocked by Gd Cl3 and streptomycin.