A Neonatal Mouse Model for Pressure Overload: Myocardial Response Corresponds to Severity

Abstract

The heart regeneration after apical resection and myocardial infarction in neonatal mice has been studied for years. However, the response of neonatal mouse heart under pressure overload is seldom explored. This study aimed to induce pressure overload in neonatal mice through a transverse aortic constriction (TAC) with different-gauge needles so as to investigate the effect of pressure overload on cardiomyocyte proliferation and hypertrophy in these mice. Myocardial hypertrophy was evaluated by echocardiographic, pathological, and molecular analyses. Cardiomyocyte proliferation was detected by immune-staining of phospho-histone H3, Ki67, and 5-bromo-2-deoxyuridine. Mild pressure overload induced with a 30-gauge needle stimulated cardiomyocyte proliferation, adaptive hypertrophy, and angiogenesis. The heart function was not hampered even 21 days after the surgery. Moderate pressure overload induced with a 32-gauge needle led to pathological myocardial hypertrophy, fibrosis, and heart failure 7 days after the surgery. The gene and protein expression levels of markers of hypertrophy and fibrosis increased in 32-gauge TAC group compared with that in sham and 30-gauge TAC groups. The mice barely survived after severe pressure overload induced with a 34-gauge needle. The findings of this study might provide new insights into cardiomyocyte proliferation and hypertrophy in neonatal mice under pressure overload.

Necroptosis Inhibition by Hydrogen Sulfide Alleviated Hypoxia-Induced Cardiac Fibroblasts Proliferation via Sirtuin 3

“…Previous studies have demonstrated that the antigen identified by the monoclonal antibody Ki67 is related to cell mitosis, while proliferating cell nuclear antigen (PCNA) plays an important role in the DNA replication processes. That is to say, both Ki67 and PCNA are sensitive indicators of cell proliferation [18,19]. Therefore, the expression of Ki67 and PCNA were also detected to evaluate the effect of NaHS on hypoxia-induced cardiac fibroblast proliferation.…”

Molecular Changes in Prepubertal Left Ventricular Development Under Experimental Volume Overload

“…We hope that, in further research, aortic valve puncture-induced VO will be created in neonatal large animals to compare with an ACF-VO model to understand the differences between these models. The RV is also more sensitive to pressure overload than the LV in terms of the cell cycle at neonatal stage ( 45 , 46 ).…”

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

“…It is also assumed that the block of mitosis in postnatal CMCs and the transition to the postmitotic phase and polyploidization of CMCs in the first weeks after birth is due to a decrease in the expression of the protein regulating CMCs cytokinesis—Ect2 and a decrease in RhoA-GTP activation [ 28 ]. In the same period, reverse regulation of cyclins and CDKs associated with the transition between the G1/S and G2/M phases and the positive regulation of cyclins and CDKs associated with the G1 phase is identified [ 18 , 20 , 21 , 23 , 27 ]. Increased expression of CDK1 and cyclin B1, as well as CDK4 and cyclin D1, induces the proliferation of fetal CMCs [ 27 ].…”

“…Other mechanisms are known to control the arrest of CMCs in the G 0 phase of the cell cycle, such as the induction of CDKs inhibitors represented by members of the INK4 family (p15, p16, p18, p19 and CIP/KIP family (p21, p27, p53, and p57) [ 17 , 18 , 19 , 21 , 22 , 23 , 24 ]. It has also been shown that the Notch signaling pathway, due to its action on cyclin D, initiates the entry into the cycle of resting embryonic stem cells and neonatal ventricular CMCs [ 125 ].…”

“…It is known that the proliferative activity of RV CMCs in patients with TF is associated with SaO 2 parameters [ 16 ]. On the other hand, in a number of experimental studies it has been shown that pressure and volume RV overload, induced in the first days of postnatal development, similar to that arising in TF, leads to the activation of the expression of proliferative markers in CMCs, as well as to increased angiogenesis and, later, myocardial fibrosis [ 17 , 18 , 19 ]. One of the unresolved questions is whether the activation of the CMCs proliferation in the immature myocardium of children with TF can be caused and by what factors.…”