A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice

Melleby, Arne Olav; Romaine, Andreas; Aronsen, Jan Magnus; Veras, Ioanni; Zhang, Lili; Sjaastad, Ivar; Lunde, Ida G.; Christensen, Geir

doi:10.1093/cvr/cvy141

Cited by 40 publications

(51 citation statements)

References 53 publications

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“…This is controlled to some extent by ligating the aorta onto a fixed gauge needle and then removing the needle. Recent developments in the TAC method employ use of an O-ring to control the tightness and degree of ligation without temporary occlusion of the aorta 30 . Another more robust TAC method 28 assesses the aortic lumen of individual mice by echocardiography to calibrate a custom-sized double loop-clip to a predefined degree of stenosis, which also reduces trauma on the aorta while improving the reproducibility of the tightness of ligation, and, thus, reducing mortality rates 28 , 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Recent developments in the TAC method employ use of an O-ring to control the tightness and degree of ligation without temporary occlusion of the aorta 30 . Another more robust TAC method 28 assesses the aortic lumen of individual mice by echocardiography to calibrate a custom-sized double loop-clip to a predefined degree of stenosis, which also reduces trauma on the aorta while improving the reproducibility of the tightness of ligation, and, thus, reducing mortality rates 28 , 30 . As the current method also employs a needle to standardize vessel diameter with uncontrolled tightening of the ligation, it is likely that these procedures could also be employed to improve rodent abdominal aortic constriction models.…”

Section: Discussionmentioning

confidence: 99%

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Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes

Nicks

Kesteven

et al. 2020

Sci Rep

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Animal models of pressure overload are valuable for understanding hypertensive heart disease. We characterised a surgical model of pressure overload-induced hypertrophy in C57BL/6J mice produced by suprarenal aortic constriction (SAC). Compared to sham controls, at one week post-SAC systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was evident by a 50% increase in the LV weight-to-tibia length ratio due to cardiomyocyte hypertrophy. As a result, LV end-diastolic wall thickness-to-chamber radius (h/R) ratio increased, consistent with the development of concentric hypertrophy. LV wall thickening was not sufficient to normalise LV wall stress, which also increased, resulting in LV systolic dysfunction with reductions in ejection fraction and fractional shortening, but no evidence of heart failure. Pathological LV remodelling was evident by the re-expression of fetal genes and coronary artery perivascular fibrosis, with ischaemia indicated by enhanced cardiomyocyte Hif1a expression. The expression of stem cell factor receptor, c-Kit, was low basally in cardiomyocytes and did not change following the development of robust hypertrophy, suggesting there is no role for cardiomyocyte c-Kit signalling in pathological LV remodelling following pressure overload.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes

Nicks

Kesteven

et al. 2020

Sci Rep

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“…Another issue raised by TAC experiment is how to maintain the consistency of the aortic constriction, which can be affected by the tightness of constriction related to suture knots and fat tissue remaining around the aorta. Melleby and colleagues constrict the aorta using an o-ring with fixed inner diameters to achieve low intra- and inter-surgeon variation ( Melleby et al., 2018 ). To guarantee the consistency of stenosis in our study, we cleared surrounding fat tissue and tightened the suture around the aorta and an overlying 27-gauge needle with two secure double overhand knots.…”

Section: Discussionmentioning

confidence: 99%

Cardiac hypertrophy or failure? - A systematic evaluation of the transverse aortic constriction model in C57BL/6NTac and C57BL/6J substrains

Stafford

Prehar

et al. 2019

Current Research in Physiology

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Background The mouse model of transverse aortic constriction (TAC) has been widely used as a cardiac stress in the investigation of the molecular mechanisms of cardiac hypertrophy. Recently, the International Knockout Mouse Consortium has selected the C57BL/6NTac (BL/6N) mouse strain to generate null alleles for all mouse genes; however, a range of genetic and cardiac phenotypic differences have been reported between this substrain and the commonly used C57BL/6J (BL/6J) substrain. It has been reported by Garcia-Menendez and colleagues that 12-week C57BL/6NTac mice are susceptible to heart failure but little is known about the cardiac remodeling in this substrain as cardiac function progresses from compensation to decompensation. Methods BL/6J and BL/6N mice were subjected to pressure overload via TAC. The impact of both age and duration of cardiac pressure overload induced by TAC on cardiac remodelling were systematically assessed. Results Our data showed that BL/6N mice developed eccentric hypertrophy with age- and time-dependent deterioration in cardiac function, accompanied by considerable interstitial fibrosis. In contrast, BL/6J mice were more resilient to TAC-induced cardiac stress and developed variable cardiac phenotypes independent of age and the duration of pressure overload. This was likely due to the greater variability in pre-TAC aortic arch dimension as measured by echocardiography. In addition to increased expression of brain natriuretic peptide and collagen gene type 1 and 3, BL/6N mice also had greater angiotensin II type 2 receptor (AT2R) gene expression than BL/6J counterparts at baseline and after 2-weeks TAC, which may contribute to the exacerbated interstitial fibrosis. Conclusions BL/6N and BL/6J mice have very different responses to TAC stimulation and these differences should be taken into consideration when using the substrains to investigate the mechanisms of hypertrophy and heart failure.

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“…Recently, a new method of constricting the ascending aorta in mice with a fixed-diameter O-ring was studied. Using O-rings with an ID of 0.61 mm or 0.66 mm, fibrosis remodeling was present at 2 weeks or 4 weeks after surgery [49]. e postoperative survival rate of ORAB was 98.7%, and only 2 of 152 cases died in the first 2 weeks after surgery [49].…”

Section: Ascending Aorta Constriction Modelmentioning

confidence: 99%

“…e main advantages of ORAB are high intra-and intersurgeon reproducibility, low postoperative mortality, and reproducible HF phenotypes [49].…”

Section: Ascending Aorta Constriction Modelmentioning

confidence: 99%

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

Ding

Wang

Jia

et al. 2020

International Journal of Hypertension

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Myocardial fibrosis is characterized by excessive deposition of myocardial interstitial collagen, abnormal distribution, and excessive proliferation of fibroblasts. According to the researches in recent years, myocardial fibrosis, as the pathological basis of various cardiovascular diseases, has been proven to be a core determinant in ventricular remodeling. Pressure load is one of the causes of myocardial fibrosis. In experimental models of pressure-overload-induced myocardial fibrosis, significant increase in left ventricular parameters such as interventricular septal thickness and left ventricular posterior wall thickness and the decrease of ejection fraction are some of the manifestations of cardiac damage. These morphological and functional changes have a serious impact on the maintenance of physiological functions. Therefore, establishing a suitable myocardial fibrosis model is the basis of its pathogenesis research. This paper will discuss the methods of establishing myocardial fibrosis model and compare the advantages and disadvantages of the models in order to provide a strong basis for establishing a myocardial fibrosis model.

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A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice

Abstract: Here, we introduce a novel method for high precision aortic constriction in mice with high intra- and inter-surgeon reproducibility and low post-operative mortality that allows generation of specific cardiac disease phenotypes.

Cited by 40 publications

References 53 publications

Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes

Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes

Cardiac hypertrophy or failure? - A systematic evaluation of the transverse aortic constriction model in C57BL/6NTac and C57BL/6J substrains

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

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