Key result
Osteopontin knockout in active NHE1 transgenic mice regressed cardiac hypertrophy, collagen deposition, CD44 upregulation, and RSK phosphorylation.
Why the study?
Does osteopontin knockout prevent cardiac hypertrophy and remodeling in mice overexpressing active NHE1?
Does osteopontin knockout prevent cardiac hypertrophy and remodeling in mice overexpressing active NHE1?
Osteopontin mediates NHE1-induced cardiac hypertrophy and remodeling, highlighting a potential mechanistic pathway involving CD44 and RSK.
Hypothesis-generating in NHE1 transgenic mice; leaves open whether osteopontin targeting translates to human cardiac disease.
exchanger isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the heart, has been demonstrated to be increased in this condition. We have previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an upregulation of myocardial osteopontin (OPN) expression. To determine the role of OPN in inducing NHE1-mediated cardiomyocyte hypertrophy, double transgenic mice expressing active NHE1 and OPN knockout were generated and assessed by echocardiography and the cardiac phenotype. Our studies showed that hearts expressing active NHE1 exhibited cardiac remodeling indicated by increased systolic and diastolic left ventricular internal diameter and increased ventricular volume. Moreover, these hearts demonstrated impaired function with decreased fractional shortening and ejection fraction. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA was upregulated, and there was an increase in heart cell cross-sectional area confirming the cardiac hypertrophic effect. Moreover, NHE1 transgenic mice also showed increased collagen deposition, upregulation of CD44 and phosphorylation of p90 ribosomal s6 kinase (RSK), effects that were regressed in OPN knockout mice. In conclusion, we developed an interesting comparative model of active NHE1 transgenic mouse lines which express a dilated hypertrophic phenotype expressing CD44 and phosphorylated RSK, effects which were regressed in absence of OPN.
No takes yet. Share an insight, caveat, or question.
Abdulrahman et al. (2018) studied Cardiac hypertrophy. Osteopontin (OPN) knockout vs. Active NHE1 transgenic mice without OPN knockout was evaluated on Cardiac hypertrophy, remodeling, and gene expression. Osteopontin knockout in active NHE1 transgenic mice regressed cardiac hypertrophy, collagen deposition, CD44 upregulation, and RSK phosphorylation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: