Application value of ultrasound in evaluating the morphological and hemodynamic changes of aorta in mice model with aortic dissection induced by angiotensinogen Ⅱcombined with β-aminopropionitrile / 中华超声影像学杂志

Objective:To observe the morphological and hemodynamics changes of aortic segments in mice with angiotensinogen Ⅱ(Ang II) combined with β-aminopropionitrile(BAPN) induced-aortic dissection by color Doppler ultrasound(CDUS).Methods:Twenty male mice of 6-8 weeks old C57BL/6 were randomly divided into two groups: the model group( n=10) was induced by intraperitoneal injection of Ang Ⅱ combined with BAPN to establish mice model with aortic dissection; the control group( n=10) was intraperitoneally injected with normal saline.The body weight, systolic and diastolic blood pressure of the mice were routinely recorded. On the 42th day, CDUS was used to measure the indexes of ascending aorta(AoA), descending thoracic aorta(DAo) and suprarenal aorta(SAo) in both groups, including the inner diameter of the cross section, peak systolic velocity(PSV), the end diastolic velocity(EDV), the resistance index(RI), the pulsatility index(PI), time average mean velocity(TAMV), the heart rate(HR) and the maximal shear rate(SR). Then, the aortas were harvested from the root to the bifurcation of the renal artery. The pathological changes of the aortic wall were observed using hematoxylin-eosin(HE) staining. Results:①There were statistically significant differences in body weight, systolic blood pressure, diastolic blood pressure and heart rate between the model group and the control group(all P<0.05). Compared with the control group(0/10), the incidence of the AoA dissection(8/10) in the model group was obviously higher, the difference was statistically significant( P<0.05); while the incidence of the DAo dissection(4/10) and the SAo dissection(3/10) in the model group was slightly higher, the differences were not statistically significant (all P>0.05). ②Compared with the ascending aorta of the control group, the inner diameter, PSV, EDV, TAMV, PI and SR in the model group were significantly higher(all P<0.05), while RI showed no significant difference between the two groups ( P>0.05). For the descending thoracic aorta, PSV, EDV, TAMV, PI and SR in model group were higher than those of the control group(all P<0.05), however the inner diameter and RI were not significantly different between the two groups (all P>0.05). And for the superior renal aorta, PSV, TAMV, RI, PI and SR in the model group were obviously higher than the control group(all P<0.05), whereas the inner diameter and EDV were not significantly different between the two groups (all P>0.05). ③The HE of the tissue section in the model group showed, the aortas were obviously dilated, irregular, with inhomogeneously thickening wall; the endothelial cell nuclei were slightly stained, and some intima and middle layer ruptured and protruded outward to form dissecting aneurysms. The adventitias were markedly infiltrated with inflammatory cells. Conclusions:Ultrasonography could primarily evaluate the hemodynamic changes of aorta in hypertension with aortic dissection, and the PSV, TAMV, PI and SR of aorta may be important indicators for early predicting the occurrence of aortic dissection in hypertension.

Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using β-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.

Induction of thoracic aortic dissection: a mini-review of β-aminopropionitrile-related mouse models / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using β-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.

Effects of alprostadil in β-aminopropanitrile induced aortic dissection in a murine model / 中华心血管病杂志

Objective: To investigate the protective role of alprostadil on aortic dissection. Methods: 26 C57BL6 male mice were divided into control group (normal drinking water, n=13) and model group (1 g·kg-1·d-1 BAPN via drinking water, n=13). On day 14, mRNA expression of inflammatory-related genes as well as EP receptor families were detected by RT-PCR (n=6 each) and EP4 protein levels were determined by Western blot (n=7 each). Another 88 mice were divided into 3 groups: control group (n=22), model group (n=33) and treatment group (n=33). The mice in model group and treatment group were applied with BAPN (1 g·kg-1·d-1) via drinking water. The mice in treatment group received additional intraperitoneal injection with alprostadil (80 μg·kg-1·d-1) for 28 days. The mice in the control and model group received equal volume intraperitoneal injection with 0.9% saline respectively. The body weight and systolic blood pressure, the mortality and morbidity were monitored from the beginning until the designed end of the study. On day 28, the mice were sacrificed and aorta were fixed, embedded and sliced, followed by staining with HE and Victoria Blue. The distribution of EP4 was determined by immunohistochemistry in control (n=6) and model group (n=6). Furthermore, the concentration of PGE1 were tested among model (n=3) and treatment group (n=4). EP4 protein expression was determined in model group (n=7) and treatment group (n=6). Results: On day 14, mRNA expression level of MCP-1 ((2.74±1.55) vs. (1.00±0.49),<0.05) and MMP2((1.38±0.42) vs. (1.00±0.27), P<0.05) was significantly upregulated in model group compared with control group. Protein expression of EP4 receptor also increased in aorta in model group compared with control group (1.48±0.51 vs. 1.00±0.19, P<0.05). In the dissection area, the EP4 expression was also enriched compared with non-dissection area, particularly in endothelial cells and inflammatory cells on day 28. BAPN applied in drinking water (model and treatment groups) successfully induced the aortic dissection in mice, some mice died of the rupture. The elastic fibers were fractured, and the infiltrated immune cells were visible in dissected tissue. False lumen was formed. There was no dissection and death in the control group. Compared with control group, the morbidity and mortality rates were significantly increased in the model group (60.6%, 20/33, 30.3%, 10/33) and the treatment group (72.7%, 24/33, 24.2%, 8/33). The mortality and morbidity rates were similar between model and treatment groups. There is no difference in terms of SBP among three groups (P>0.05). Further study showed that after alprostadil injection, the blood concentration of PGE1 was increased in treatment group ((0.540±0.041 vs. 0.436±0.012)μmol/L, P<0.05). Besides, the EP4 receptor expression was downregulated in the treatment group compared to model group (0.60±0.30 vs. 1.00±0.20, P<0.05). Conclusion: EP4 expression is upregulated in BAPN induced aortic dissection mouse model. No protective effects are observed post alprostadil treatment in this model probably due to the reduced expression of EP4.

Establishment of a mouse model of aorta dissection induced by β-aminopropionitrile drinking combined with angiotensin II infusion / 中国实验动物学报

Objective To establish a mouse model of aorta dissection (AD) by β-aminopropionitrile (BAPN) in drinking water + subcutaneously pumped angiotensin II (Ang II) infusion.Methods Forty 3-week-old C57B1/6J male mice were randomly divided into two groups.All animals received 0.1 g/kg/d BAPN in drinking water for 4 weeks.Then the BAPN drinking + saline infusion group and BAPN drinking + Ang II infusion group received continuous saline or Ang II (1,000 ng/kg/min) infusion, respectively, via subcutaneous osmotic minipump for 72 hour.The mice were restricted in a noninvasive computerized tail-cuff system and their arterial systolic blood pressure and heart rate were monitored.Autopsy was performed if a mouse died during the experiment.At the end of the experiment, mice were sacrificed by injection with an overdose of sodium pentobarbital and the aortas were harvested.The formation of aortic false lumen was observed by pathology using hematoxylin-eosin staining.Results The overall incidence of AD in the BAPN drinking administration +Ang II infusion group was 95%, whereas the incidence of AD in the BAPN drinking administration +saline infusion group was only 5%.The mortality from dissecting aneurysm rupture was 24% in the BAPN drinking administration +Ang II infusion group during the experiment.Pathological examination of the aortic cross-sections clearly showed the formation of blood-filled false lumens induced by Ang II.Conclusions A mouse model with high incidence of aortic dissection is successfully established.