Table 3. Influence of pharmacological NLRP3 inflammasome inhibition on experimental AAAs.
Animal species and strain | AAA model | Intervention | Influence on experimental AAAs | References |
---|---|---|---|---|
Wild type Sprague- Dawley rats | Calcium chloride | NLRP3 inhibitor (Tranilast) |
•Reduced aneurysmal aortic dilation and preserved medial elastin •Attenuated aortic infiltration of mast cells and T cells •Reduced aortic MMP activity |
[89] Tsuruda T et al. Circ Res 102: 1368-1377, 2008. |
ApoE -/- mice | Ang II infusion | Pan-caspase inhibitor (Quinoline- Val-Asp difluorophenoxymethylketone) |
•Reduced aneurysm diameter and incidence •Inhibited cell apoptosis and reduced macrophage infiltration |
[88] Yamanouchi D et al. Arterioscler Thromb Vasc Biol 30: 702-707, 2010. |
Wild type C57BL/6 mice | Calcium chloride | ROS scavenger (Resveratrol) |
•Inhibited AAA formation •Reduced inflammatory cell infiltration and aortic expression of MMPs, MCP-1 and TNF-α |
[99] Kaneko H et al. Atherosclerosis 217: 350- 367, 2011. |
Wild type Sprague- Dawley rats | Elastase infusion | ROS scavenger (Resveratrol) |
•Reduced aneurysmal size •Reduced systemic and aortic levels of TNF-α and MMP9 •Reduced circulating L-selectin-expressing monocytes and aortic macrophages |
[100] Palmieri D et al. J Surg Res 171: e237-e246, 2011. |
ApoE -/- mice | Ang II infusion | Dipeptidyl peptidase-4 inhibitor (sitagliptin) | •Inhibited AAA formation, reduced aortic inflammation and preserved elastin lamina | [94] Lu HY et al. Plos One 10: e0121077, 2015. |
ApoE -/- mice | Ang II infusion and high fat diet | Dipeptidyl peptidase-4 inhibitor (MK0626) |
•Reduced aneurysm diameter and incidence •Reduced aortic IL-1β mRNA levels but increased aortic TIMP-2 mRNA levels |
[96] Kohashi K et al. J Atheroscler Thromb 23: 441- 454, 2016. |
Wild type Sprague- Dawley rats | Intra-aortic Elastase infusion and abluminal calcium chloride application | Glucagon-like peptide 1 receptor analog (lixisenatide) |
•Attenuated aneurysmal aortic dilation and macrophage infiltration but increased aortic elastin contents •Reduced aortic ROS production, oxidative DNA damage and ERK phosphorylation •Reduced the aortic mRNA levels of MMP9 and TNF-α |
[93] Yu J et al. Surgery Today 46: 1099-1107, 2016. |
Wild type C57BL/6 mice | Ang II infusion and high fat diet | NLRP3 inhibitor (Glyburide) | •Reduce aneurysmal aortic diameter, aneurysm incidence and elastin destruction |
[87] Wu D et al. Arterioscler Thromb Vasc Biol 37: 694- 706, 2017. |
ApoE -/- mice | Ang II infusion and high fat diet | ROS scavenger (Resveratrol) |
•Reduced aneurysmal aortic diameter •Increased the expression levels of aortic ACE2 and SIRT1 •Reduced the phosphorylation of AKT1 and ERK1/2 as well as the expression levels of Ang II type-1 receptor, MMP2 and MMP9 |
[98] Moran CS et al. Arterioscler Thromb Vasc Biol 37: 2195-2203, 2017. |
ApoE -/- mice | Ang II infusion and high fat diet | Dipeptidyl peptidase-4 inhibitor (teneligliptin) |
•Suppressed aneurysmal aortic expansion, reduced aneurysm severity, and lowered aneurysm incidence •Attenuated medial elastin degradation and macrophage infiltration •Reduced MMP activity, the phosphorylation of AKT and ERK and IL-6 mRNA levels in aneurysmal aorta |
[97] Takahara Y et al. J Atherioscler Thromb 25: 698-708, 2018. |
Wild type C57BL/6 mice | Ang II infusion and high fat diet | NLRP3 inhibitor (MCC950) |
•Reduced aortic diameter, aneurysm/ dissection rate and macrophage accumulation •Reduced aortic expression of active IL-1β and caspase 1 as well as MMP activity |
[84] Ren P et al. J am Heart Assoc 9: e014044, 2020. |
AAA: Abdominal aortic aneurysm. ACE2: Angiotensin-converting enzyme 2. AKT1: Rac-alpha serine/threonine-protein kinase or protein kinase B. Ang II: Angiotensin II. ApoE: Apolipoprotein E. ERK: Extracellular-signal-regulated kinase. IL: Interleukin. MMPs: Matrix metalloproteinases. MCP: Monocyte chemotactic protein. ROS: Reactive oxygen species. SIRT1: Silent mating type information regulation 2 homolog 1. TNF: Tumor necrosis factor. -/-: Deficient mice