Distinct Phenotypes Induced by Different Degrees of Transverse Aortic Constriction in C57BL/6N Mice

Deng, Hongsheng; Ma, Liang; Kong, Fanhua; Qiao, Zhihua

doi:10.3389/fcvm.2021.641272

Cited by 11 publications

(16 citation statements)

References 30 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Use of 27 gauge (27G) needles result in severe cardiac impairment and HFrEF in larger mice. 77 However, there is evidence that suture-based TAC using the same 27G spacer, but various suture materials (silk versus monofil) for constriction resulted in a relative high LV mass variation and changes in LVEF. This might be due to different self-elastic quality of the sutures.…”

Section: Small Animal Models Of Pressure Overloadmentioning

confidence: 99%

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Pilz

Chang

Kiss

et al. 2022

Circulation Research

View full text Add to dashboard Cite

Heart failure (HF) describes a heterogenous complex spectrum of pathological conditions that results in structural and functional remodeling leading to subsequent impairment of cardiac function, including either systolic dysfunction, diastolic dysfunction, or both. Several factors chronically lead to HF, including cardiac volume and pressure overload that may result from hypertension, valvular lesions, acute, or chronic ischemic injuries. Major forms of HF include hypertrophic, dilated, and restrictive cardiomyopathy. The severity of cardiomyopathy can be impacted by other comorbidities such as diabetes or obesity and external stress factors. Age is another major contributor, and the number of patients with HF is rising worldwide in part due to an increase in the aged population. HF can occur with reduced ejection fraction (HF with reduced ejection fraction), that is, the overall cardiac function is compromised, and typically the left ventricular ejection fraction is lower than 40%. In some cases of HF, the ejection fraction is preserved (HF with preserved ejection fraction). Animal models play a critical role in facilitating the understanding of molecular mechanisms of how hearts fail. This review aims to summarize and describe the strengths, limitations, and outcomes of both small and large animal models of HF with reduced ejection fraction that are currently used in basic and translational research. The driving defect is a failure of the heart to adequately supply the tissues with blood due to impaired filling or pumping. An accurate model of HF with reduced ejection fraction would encompass the symptoms (fatigue, dyspnea, exercise intolerance, and edema) along with the pathology (collagen fibrosis, ventricular hypertrophy) and ultimately exhibit a decrease in cardiac output. Although countless experimental studies have been published, no model completely recapitulates the full human disease. Therefore, it is critical to evaluate the strength and weakness of each animal model to allow better selection of what animal models to use to address the scientific question proposed.

show abstract

Section: Small Animal Models Of Pressure Overloadmentioning

confidence: 99%

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Pilz

Chang

Kiss

et al. 2022

Circulation Research

View full text Add to dashboard Cite

show abstract

“…TAC-treated mice develop cardiac hypertrophy, cardiac fibrosis, inflammation, and eventually cardiac dilation and HF. The progression of this adverse cardiac remodeling induced by TAC is associated with the duration of aortic constriction ( 9 , 13 ). However, very few studies observed a time-series cardiac remodeling phenotype induced by TAC ( 11 , 20 , 21 ), especially in C57BL/6 J mice applied with a 25-gauge needle.…”

Section: Resultsmentioning

confidence: 99%

“…The constriction degree of the aorta arch is the most important factor affecting the phenotypes of TAC-induced cardiac remodeling. The constriction diameter of the needles used for TAC varied from 17-gauge to 30-gauge, but a 27-gauge needle has been the most common needle size (>70%) for constriction in TAC study ( 9 , 10 , 13 , 16 , 28 ). Several studies have compared the resulting phenotypes to different needles, including 25-gauge, 26-gauge, and 27-gauge needles ( 9 , 11 ).…”

Section: Discussionmentioning

confidence: 99%

A time-series minimally invasive transverse aortic constriction mouse model for pressure overload-induced cardiac remodeling and heart failure

Wang

Zhu²,

Li³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Transverse aortic constriction (TAC) is a widely-used animal model for pressure overload-induced cardiac hypertrophy and heart failure (HF). The severity of TAC-induced adverse cardiac remodeling is correlated to the degree and duration of aorta constriction. Most studies of TAC are performed with a 27-gauge needle, which is easy to cause a tremendous left ventricular overload and leads to a rapid HF, but it is accompanied by higher mortality attributed to tighter aortic arch constriction. However, a few studies are focusing on the phenotypes of TAC applied with a 25-gauge needle, which produces a mild overload to induce cardiac remodeling and has low post-operation mortality. Furthermore, the specific timeline of HF induced by TAC applied with a 25-gauge needle in C57BL/6 J mice remains unclear. In this study, C57BL/6 J mice were randomly subjected to TAC with a 25-gauge needle or sham surgery. Echocardiography, gross morphology, and histopathology were applied to evaluate time-series phenotypes in the heart after 2, 4, 6, 8, and 12 weeks. The survival rate of mice after TAC was more than 98%. All mice subjected to TAC maintained compensated cardiac remodeling during the first two weeks and began to exhibit heart failure characteristics after 4 weeks upon TAC. At 8 weeks post-TAC, the mice showed severe cardiac dysfunction, hypertrophy, and cardiac fibrosis compared to sham mice. Moreover, the mice raised a severe dilated HF at 12 weeks. This study provides an optimized method of the mild overload TAC-induced cardiac remodeling from the compensatory period to decompensatory HF in C57BL/6 J mice.

show abstract

“…TAC can induce left ventricle systolic dysfunction and cardiac remodeling in mice ( 23 ). The results of previous experiments on the conditional increase/decrease in HIF-1α expression observed in mice following TAC surgery appear to be contradictory.…”

Section: Discussionmentioning

confidence: 99%

“…The TAC and CIH exposure protocols were approved by the Animal Experiment Ethics Committee of Southeast University School of Medicine. The afterload stress mouse model was established as reported ( 23 ). In short, mice were anesthetized with isoflurane (3% isoflurane for induction, 2% isoflurane for maintenance).…”

Section: Methodsmentioning

confidence: 99%

Chronic intermittent hypoxia accelerates cardiac dysfunction and cardiac remodeling during cardiac pressure overload in mice and can be alleviated by PHD3 overexpression

Zhen

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Obstructive sleep apnea (OSA) accelerates the progression of chronic heart failure (CHF). OSA is characterized by chronic intermittent hypoxia (CIH), and CIH exposure accelerates cardiac systolic dysfunction and cardiac remodeling in a cardiac afterload stress mouse model. Mechanistic experiments showed that long-term CIH exposure activated hypoxia-inducible factor 1α (HIF-1α) expression in the mouse heart and upregulated miR-29c expression and that both HIF-1α and miR-29c simultaneously inhibited sarco-/endoplasmic reticulum calcium ATPase 2a (SERCA2a) expression in the mouse heart. Cardiac HIF-1α activation promoted cardiomyocyte hypertrophy. SERCA2a expression was suppressed in mouse heart in middle- and late-stage cardiac afterload stress, and CIH exposure further downregulated SERCA2a expression and accelerated cardiac systolic dysfunction. Prolyl hydroxylases (PHDs) are physiological inhibitors of HIF-1α, and PHD3 is most highly expressed in the heart. Overexpression of PHD3 inhibited CIH-induced HIF-1α activation in the mouse heart while decreasing miR-29c expression, stabilizing the level of SERCA2a. Although PHD3 overexpression did not reduce mortality in mice, it alleviated cardiac systolic dysfunction and cardiac remodeling induced by CIH exposure.

show abstract

Distinct Phenotypes Induced by Different Degrees of Transverse Aortic Constriction in C57BL/6N Mice

Cited by 11 publications

References 30 publications

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

Large and Small Animal Models of Heart Failure With Reduced Ejection Fraction

A time-series minimally invasive transverse aortic constriction mouse model for pressure overload-induced cardiac remodeling and heart failure

Chronic intermittent hypoxia accelerates cardiac dysfunction and cardiac remodeling during cardiac pressure overload in mice and can be alleviated by PHD3 overexpression

Contact Info

Product

Resources

About