Female Mice Exhibit Abdominal Aortic Aneurysm Protection in an Established Rupture Model

Fashandi, Anna Z.; Spinosa, Michael; Salmon, Morgan; Su, Gang; Montgomery, William G.; Mast, Alexis; Lu, Guanyi; Hawkins, Robert B.; Cullen, J. Michael; Sharma, Ashish K.; Ailawadi, Gorav; Upchurch, Gilbert R.

doi:10.1016/j.jss.2019.10.004

Cited by 20 publications

(14 citation statements)

References 22 publications

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“…In this study, in the elastase combined with calcium chloride group, the success rate of the operation was 100%, the survival rate was 90%, the total aneurysm formation rate was 80%, the male aneurysm formation rate was 100%, and the female aneurysm formation rate was 60%. Consistent with the epidemiological investigation of human AAA, the incidence rate of males was higher than that of females ( 20 ). The model has good stability and is suitable for studying the pathogenesis of AAA.…”

Section: Discussionsupporting

confidence: 84%

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Zhu

Tang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundConstructing an ideal model of abdominal aortic aneurysm (AAA) is of great significance to elucidate its complex pathogenesis. Therefore, we introduce a new and simple method to simulate human AAA and construct a rat AAA model through a retroperitoneal approach.MethodsForty healthy adult Sprague Dawley (SD) rats were randomly divided into a control group, elastase + calcium chloride group (PPE+CaCl2), elastase group (PPE), and elastase + beta aminopropionitrile group (PPE+BAPN) according to a male-female ratio of 1:1, with 10 rats in each group. A retroperitoneal approach was used to free the infrarenal abdominal aorta in all four groups. In the PPE + CaCl2 group, 0.1 ml of elastase (approximately 5 U) was perfused into the arterial cavity for 20 min, and 1.0 mol/L calcium chloride was infiltrated out of the arterial cavity for 10 min. In the PPE group, 0.1 mL of elastase (approximately 5U) was perfused into the arterial cavity for 20 min, and normal saline was infiltrated out of arterial cavity for 10 min; the PPE + BAPN group combined with 0.3% BAPN drinking water/day on the basis of PPE group; the control group was treated with saline instead of elastase and calcium chloride. Abdominal aortic specimens were collected after 4 weeks of feeding. The diagnostic criteria of AAA were 50% dilation of the abdominal aorta or rupture of the aneurysm at 4 weeks after the operation. Histopathology, immunohistochemistry, quantitative PCR (qPCR), western blotting assay, gelatine zymogram, and other methods were used.ResultsThe operation time of the four groups was controlled at approximately 40 min, and the success rate of the operation was 100%. Survival rate: Control Group (100%) = PPE Group (100%) > PPE + CaCl2 Group (90%) > PPE + BAPN Group (40%); Aneurysm formation rate: PPE + BAPN Group (100%) > PPE + CaCl2 Group (80%) > PPE Group (60%) > Control Group (0%); Aneurysm rupture rate: PPE + BAPN group (60%) > PPE + CaCl2 group (12.5%) > PPE group (0%);Inflammatory cells (macrophages, T cells, B cells, dendritic cells) infiltrated in different degrees in the PPE + CaCl2, PPE and PPE + BAPN groups. Vascular thickness, elastic fiber content, collagen fiber content, and vascular smooth muscle cell content in the PPE + CaCl2 group and PPE + BNPA group were significantly lower than those in Control group (P < 0.05). The content of elastic fibers and vascular smooth muscle cells in the PPE group were significantly lower than that in Control group (P < 0.05). The expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the PPE + CaCl2 group, PPE group, and PPE + BNPA group were significantly higher than those in the control group (P < 0.05).ConclusionsA new, simple, and reproducible rat AAA model can be constructed by a retroperitoneal approach. The pathological features of the three models are effective simulation of human AAA inflammatory cell infiltration, protease activity enhancement, and extracellular matrix destruction. The PPE+ CaCl2 model has the advantages of a high survival rate, high aneurysm formation rate, good stability, and reproducibility. It is an ideal animal model for studying the pathogenesis of AAA. The PPE + BAPN model can simulate the characteristics of spontaneous rupture of aneurysms. It is an ideal animal model to study the mechanism of AAA rupture.

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Section: Discussionsupporting

confidence: 84%

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Zhu

Tang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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“…Male sex has long been accepted as a risk factor for AAA, as the prevalence of AAA was 4:1 in males compared with females (73,228). Compared with male mice, female mice exhibit lower AAA rupture rates and decreased SMCs degradation (73). Androgen receptor promotes the development of AAA in mice through IL-1␣ and TGF-␤1 (103).…”

Section: Aneurysmmentioning

confidence: 99%

Metabolism of vascular smooth muscle cells in vascular diseases

Shi

Yang

Cheng

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

194

120

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Vascular smooth muscle cells (VSMCs) are the fundamental component of the medial layer of arteries and are essential for arterial physiology and pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill the bio-energetic and biosynthetic requirements. During vascular injury, VSMCs switch from a quiescent "contractile" phenotype to a highly migratory and proliferative "synthetic" phenotype. Recent studies find that the phenotype switching of VSMCs is driven by a metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, have distinct, indispensable roles in normal and dysfunctional vasculature. VSMCs metabolism is also related to the metabolism of endothelial cells. In the present review, we present a brief overview of VSMCs metabolism, and how it regulates the progression of several vascular diseases, including atherosclerosis, systemic hypertension, diabetes, pulmonary hypertension, vascular calcification, and aneurysms, and the effect of the risk factors for vascular disease (aging, cigarette smoking and excessive alcohol drinking) on VSMCs metabolism, to clarify the role of VSMCs metabolism in the key pathological process.

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“…Fashandi et al demonstrated in a mouse model that female mice had decreased AAA rupture rates (16% vs. 46%; P = .029) [17]. Female mice expressed fewer elastin breaks (P = .0079) and decreased smooth muscle cell degradation (P = .0057).…”

Section: Pathophysiologymentioning

confidence: 98%

Aneurysms and dissections - What is new in the literature of 2019/2020 - a European Society of Vascular Medicine annual review

Nikol

Mathias²,

Olinic

et al. 2020

Vasa

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Female Mice Exhibit Abdominal Aortic Aneurysm Protection in an Established Rupture Model

Cited by 20 publications

References 22 publications

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Metabolism of vascular smooth muscle cells in vascular diseases

Aneurysms and dissections - What is new in the literature of 2019/2020 - a European Society of Vascular Medicine annual review

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