Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice

Abstract

Transverse aortic constriction (TAC) is a well-established model of pressure overload-induced cardiac hypertrophy and failure in mice. The degree of constriction “tightness” dictates the TAC severity and is determined by the gauge (G) of needle used. Though many reports use the TAC model, few studies have directly compared the range of resulting phenotypes. In this study adult male mice were randomized to receive TAC surgery with varying degrees of tightness: mild (25G), moderate (26G) or severe (27G) for 4 weeks, alongside sham-operated controls. Weekly echocardiography and terminal haemodynamic measurements determined cardiac remodelling and function. All TAC models induced significant, severity-dependent left ventricular hypertrophy and diastolic dysfunction compared to sham mice. Mice subjected to 26G TAC additionally exhibited mild systolic dysfunction and cardiac fibrosis, whereas mice in the 27G TAC group had more severe systolic and diastolic dysfunction, severe cardiac fibrosis, and were more likely to display features of heart failure, such as elevated plasma BNP. We also observed renal atrophy in 27G TAC mice, in the absence of renal structural, functional or gene expression changes. 25G, 26G and 27G TAC produced different responses in terms of cardiac structure and function. These distinct phenotypes may be useful in different preclinical settings.

Therapeutic Potential of Centella asiatica and Its Triterpenes: A Review

“…Pressure overload triggers the expression of inflammation genes. Inhibiting early inflammation reactions can reduce cardiac remodeling and improve heart function ( Suetomi et al, 2018 ; Richards et al, 2019 ). Fibrosis is a pivotal player in the development and progression of heart failure, which is controlled by the TGF-β/Smads pathway.…”

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

“…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.…”

Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload

“…Two-dimensional color Doppler imaging was used to demonstrate laminar blood flow in the sham group and turbulent blood flow in the TAC group on the aortic arch. Pulsed-wave Doppler was used to measure the velocity of the blood flow in the aortic arch, and the pressure gradient in the arch was calculated using the modified Bernoulli equation (Pressure gradient = 4 × velocity 2 )[21].…”