The experimental model of transition from compensated cardiac hypertrophy to failure created by transverse aortic constriction in mice

Abstract

BackgroundTransverse aortic constriction (TAC) operation is used as an experimental model of left ventricular (LV) hypertrophy and LV failure in mice. The severity of LV remodeling or failure may depend on the degree of TAC, but is variable among operated animals. Therefore, we tried to identify the optimal diameter of TAC to create this model with ease and high reproducibility.Methods and resultsTo produce TAC in C57BL/6J mice (7–9 weeks, body weight 19–26 g, n = 109), a 7–0 nylon suture ligature was tightly tied around the transverse aorta against needles with 3 different diameters (mm); 0.40, 0.385 and 0.375. LV wall thickness, end-diastolic dimension, fractional shortening were measured by echocardiography. At 4 weeks after TAC, no mouse with the 0.400 mm gauge progressed in LV failure. The 0.385 mm pin gauge mouse kept a more survival rate compared with the 0.375 mm (59% vs 48%), representing same efficient in LV failure. With the 0.385 mm pin gauge, hearts of mice remained LV hypertrophy at 1 week after TAC, followed by LV failure at 4 weeks.ConclusionTAC with the diameter of 0.385 mm can effectively induce the transition from LV hypertrophy to failure in mice with relatively preserved survival.

Inhibition of Interleukin‐6/glycoprotein 130 signalling by Bazedoxifene ameliorates cardiac remodelling in pressure overload mice

“…The compensatory cardiac hypertrophy at early stage of TAC‐induced pathology might account for the reason why TAC negatively effects and Bazedoxifene shows cardioprotective effect on heart function only significantly at 8 weeks after surgery in our study, which suggested that although the pharmacological intervention and insult all started in the initial phases, the redefined trajectory of disease progression might be identified in a long‐term period. Intriguingly, Furihata et al found operation with a 0.400 mm gauge needle led to the state of hypertrophy without left ventricular dysfunction at 4 weeks after surgery, in which the authors also showed that the 0.385 mm and 0.375 mm group (smaller constriction diameter than that in our study) of mice represented efficient in left ventricular failure at 4 weeks, while the average bodyweight of mice (19‐26 g) in the research was lower than that in our study. In another study Richards et al reported that TAC mice using a 27 gauge blunt needle (smaller constriction diameter than 0.400 mm) developed significant cardiac dysfunction, however, the important point of note they found was the cardiac response to different degrees of constriction seemed not to be quite consistent with the severities of phenotype because the exacerbation of several cardiac parameters was not step‐wise such as fractional shortening, ejection fraction, left atrial area, etc These reports indicate the underlying mechanisms governing these distinct responses to TAC in murine heart under different degrees of insult are still not clear, which deserves further study to figure out the potential reasons.…”

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

“…ORAB allows for grading of aortic constriction, leading to distinct cardiac patho-phenotypes important for studies of clinically relevant types of HF. In comparable suture-based TAC studies, 14,46 constriction using needles with decreasingly smaller diameter has been tested. However, the variation in suture tightening resulted in relatively high mortality due to acute HF in all groups within 2 weeks of surgery, despite the different sizing needles.…”

The disruption of invariant natural killer T cells exacerbates cardiac hypertrophy and failure caused by pressure overload in mice

“…The transverse aortic constriction (TAC) procedure was performed in WT (WT+TAC; n = 15) or KO (KO+TAC; n = 22) mice as described by Furihata et al. (2016). Briefly, after being anaesthetized with an i.p .…”

“…From the LV tissues, 5‐μm‐thick sections were cut and stained with Masson's Trichrome. The myocyte cross‐sectional area and collagen volume fraction were determined as previously described (Furihata et al., 2016; Homma et al., 2013; Sobirin et al., 2012).…”

“…Cell lysis and immunoblotting were performed as previously described (Furihata et al., 2016; Homma et al., 2013; Sobirin et al., 2012). Equal amounts of protein extracted from LV tissue were separated by SDS‐PAGE, transferred to nitrocellulose membranes and blotted with rabbit polyclonal antibodies against phospho‐extracellular signal‐regulated kinase (p‐ERK1/2), phospho‐c‐Jun N‐terminal kinase (p‐JNK), phospho‐p38 mitogen‐activated protein kinase (p‐MAPK), phospho‐signal transducer and activator of transcription 3 (p‐STAT3) and human antigen R (HuR; Millipore, Billerica, MA, USA).…”