Kunming mouse strain is less susceptible to elastase‐induced abdominal aortic aneurysms

Abstract

Background Porcine pancreatic elastase (PPE) is successfully used to induce abdominal aortic aneurysm (AAA) in mice. However, differences between mouse strains in susceptibility to PPE induction have been reported. Kunming mouse is one of the most frequently used strains in China but whether it is suitable for induction of AAA by PPE application remains unclear. Methods PPE infusion (1.5 units/ml) in temporary controlled aorta was performed to induce AAAs in both C57BL/6J and Kunming mice. Phosphate‐buffered saline (PBS) application was used as vehicle control. The aorta diameters of all mice were measured at days 0 and 14 after surgery to evaluate the AAA formation. Results After 14 days of PPE or PBS infusion, all mice were sacrificed and aorta tissues were collected for histological staining analysis. At the 14th day after infusion, PPE successfully induced aortic dilation in Kunming mice and typical AAA in C57BL/6J mice. The aorta diameter increased by 0.23 mm in Kunming mice after PPE infusion, while it was 0.72 mm in the C57BL/6J strain. PPE induced mild elastin degradation, smooth muscle cell (SMC) depletion and mural leucocyte infiltration in Kunming mice, but in PPE‐sensitive C57BL/6J mice, it induced total loss of SMCs, elastin disappearance and diffused infiltrated leucocytes in aortic aneurysmal segments. The effects of PPE in inducing angiogenesis and upregulating matrix metalloproteinase 2 and 9 expression in Kunming mice were also weaker than that in C57BL/6J mice. Conclusion At the reported dose of PPE, Kunming mouse is not as susceptible to AAA formation as C57BL/6J mice. The failure of PPE to induce AAA formation in Kunming mice may be associated to its inability to boost a strong inflammatory response.

Genetic deficiency of protein inhibitor of activated STAT3 suppresses experimental abdominal aortic aneurysms

“…Experimental AAAs were induced in PIAS3 −/− and PIAS3 +/+ mice by transient luminal infusion of porcine pancreatic elastase (PPE, 1.5 units/mL in phosphate-buffered saline) in controlled infrarenal aortic segment as previously reported ( 16 , 17 ). Briefly, 9–12 weeks old male mice were anesthetized by 2% isoflurane inhalation, and infrarenal aorta was exposed via a laparotomy.…”

“…Frozen sections were stained with hematoxylin and eosin (H & E) and Elastic van Gieson (EVG) stains, respectively, for the assessment of general morphology and elastin integrity. Aortic media elastin degradation was graded as I (mild) to IV (severe) on EVG-stained sections as previously reported (16)(17)(18)(19)(20). To evaluate SMC depletion, acetonefixed frozen sections were stained with a goat anti-SMC α-actin antibody followed a standard biotin-streptavidin peroxidase procedure.…”

Small AAAs: Recommendations for Rodent Model Research for the Identification of Novel Therapeutics

“…26,30 Aneurysm rupture is not a feature of this model, and AAA induction with intraluminal perfusion is technically challenging to learn. [34][35][36] Adventitial exposure of the aorta to calcium chloride (calcium phosphate or elastase) is a less complex way to induce AAA. 31,39 This model develops true aneurysms, with adventitial inflammation and matrix remodeling, but there is no intraluminal thrombus, and aortic expansion is small and usually limited to about 2 weeks, and aortic rupture does not occur (Tables 1 and 2).…”

“…[13][14][15][16][17][18][20][21][22][23][24][25][26][27]30,31,39 Ultrasound imaging is the recommended outcome as it allows aneurysms to be established before the initiation of aneurysm-modifying therapy and for expansion to be monitored by repeat changes in aortic diameter as in patients. The exact aortic diameter measurement method used and the reproducibility of this key outcome should [16][17][18]32 Elastase (a) and TGFβ blocking antibody (IP) 19 Ang II (SC) [20][21][22][23][24][25][26][27][28][29]33 Elastase (l) 26,30,[34][35][36] Calcium chloride (a) 31,37,38 Mimics human pathology (details in The rating for the aspects shown in Table 2 is aligned to the scoring in Table 1. For example, for mimics human pathology models scoring ++ have yes and those with + to <++ partly, similarly for mimics human disease progression models scoring ++ well and 0 poorly.…”

“…Abdominal aortic aneurysm (AAA) is a focal dilatation of the abdominal aorta diagnosed by imaging (maximal diameter, ≥30 mm). 1 Modest aortic dilation (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) mm in women and 30-54 mm in men) is usually asymptomatic and is only rarely complicated by rupture. 2 Larger AAAs have aortic rupture risks exceeding 5% per year 3 and are estimated to be responsible for ≈200 000 deaths worldwide annually.…”