In the in vivo experiment, Ang-(1-7) treatment reduced the incidence and severity of AAA induced by Ang II infusion, and the mechanisms involved inhibited macrophage infiltration, attenuated expression of interleukin 6(IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1(MCP-1) and matrix metalloprotease 2(MMP2), as well as abated SMCs apoptosis in the abdominal aortic tissues.
This study demonstrates that HMet may exacerbate the formation of AAA due to the increased dilation ratio partially via enhancing MMP-2 and inflammatory responses.
These data indicate the potential for excess Hcy to enhance damage of arterial wall in thinner AAA segments as a result of the increased activity of MMP-2 and fibrinolytic factors.
On the one hand, MMP-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated AAA group.
Transfection of the Egr-1 specific synthetic DNA enzyme EDRz significantly reduced AAA following elastase infusion in rats, at least in part due to the decreased expression of downstream MMP-2 and MMP-9.
We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development.
In vitro study showed that treating VSMCs with TNF-α together with DOX remarkably inhibited the expressions and activities of MMPs (MMP-2 and MMP-9), significantly suppressed the activation of protein kinase B (AKT) signaling pathway and mitogen-activated protein kinases (MAPKs) signal proteins, including extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinases (JNK) and p38, and downregulated mRNA levels of interleukin-6 (IL-6) and monocyte chemotactic protein 1 (MCP-1), and significantly upregulated mRNA levels of transforming growth factor beta (TGF-β), heme oxygenase 1 (HO-1) and superoxide dismutase 1 (SOD-1), indicating that DOX inhibits activities of MMPs through reducing oxidative stress, suppressing MAPKs and AKT signaling pathways and ameliorating inflammation in VSMCs, and therefore, exerts preventive as well as therapeutic effects on AAA.
Our findings suggested that miR-516a-5p may regulate MTHFR, MMP-2, and TIMP-1 expressions in human VSMCs, possibly promoting the disruption of Hcy metabolism and proteolytic degradation of elastin for AAA formation.
MMP2 and -9) overexpressed within AAAs is insufficient to arrest AAA growth, since resident smooth muscle cells (SMCs) are poorly elastogenic and cannot overcome elastolysis to reinstate a healthy elastic matrix.
The findings promoted us to test whether aneurysmal prone factors could up-regulate the expression of MMP-2 and MMP-9 through aberrantly increased HIF-1α and promote AAA development.
MMP-2/-9 are involved in AAA progression and their mRNA levels in AAA-MSCs resulted higher than healthy MSCs (cMSCs), especially MMP-9 (400-fold increased).
We found a significant association with an increased risk of AAA for MMP3 (AAA patients n = 1258, controls n = 1406: OR = 1.48 [95% CI = 1.23-1.78], I(2) = 0%) and MMP-13 (AAA patients n = 800, controls n = 843: OR = 1.37 [95% CI = 1.04-1.82], I(2) = 25%) polymorphisms and a trend that did not reach the statistical significance, toward a decreased risk of AAA for MMP2 (AAA patients n = 1090, controls n = 1077: OR = 0.83 [95% CI = .60-1.15], I(2) =7 1%) and ELN (AAA patients n = 904, controls n = 1069: OR = 0.79 [95% CI = .53-1.18], I(2) = 72%) polymorphisms.
Males formed larger AAAs at d 14 compared with females (P < 0.001), with significantly higher levels of JNK1 protein, proMMP9, proMMP2, and active MMP2.
Downregulation of remodelling enzymatic activity induced by an angiotensin-converting enzyme inhibitor (perindopril) reduces the degeneration of experimental abdominal aortic aneurysms in a rat model.
Our analysis of the entire coding region and three parts of the promoter of the MMP2 gene failed to show an association between genetic polymorphisms and AAA, suggesting that variations in the MMP2 gene do not contribute to the development of AAA.