Neuregulin-1 enhances cell-cycle activity, delays cardiac fibrosis, and improves cardiac performance in rat pups with right ventricular pressure load

Bossers, Guido P L; Dipl-Ing, Marie Günthel; Feen, Diederik E. van der; Hagdorn, Quint A.J.; Koop, Anne-Marie C.; Duijvenboden, Karel van; Barnett, Phil; Borgdorff, M. A. J.; Christoffels, Vincent M.; Silljé, Herman H W; Berger, Rolf M. F.; Bartelds, Beatrijs

doi:10.1016/j.jtcvs.2021.10.045

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…After birth, cardiomyocyte proliferation capacity is lost in mammals as a result of several postnatal processes, such as changes in oxygen levels and the transition from placental to enteral nutrition ( 91 ). However, recent studies have shown that cardiomyocytes retain the potential to proliferate after birth when under stress ( 12 , 92 ).…”

Section: Histopathology: What Do We Know?mentioning

confidence: 99%

“…Cardiomyocyte proliferation promotes adaptation to pressure overload better than cellular hypertrophy ( 92 – 95 ). Stimulating proliferation in mature cardiomyocytes or prolonging proliferative capacity after birth is therefore an attractive treatment target to preserve function of the overloaded RV.…”

Section: Histopathology: What Do We Know?mentioning

confidence: 99%

“…Cell cycle activity can also be stimulated by administration of neuregulin-1. In both mature and weaning rats with RV pressure overload, neuregulin-1 attenuated maladaptive remodeling, with improved systolic and diastolic RV function ( 92 , 94 , 95 ). It is important to note that postnatal cardiomyocyte proliferation requires high oxidative energy metabolism ( 97 ).…”

Section: Histopathology: What Do We Know?mentioning

confidence: 99%

“…Chronic PR will probably remain a culprit for as long as it takes for growing tissue valves to become available. Until then, treatment strategies could/should focus on reinforcing adaptive processes of RV remodeling in order to better accommodate adverse loading ( 92 , 96 ).…”

Section: Current and Future Strategiesmentioning

confidence: 99%

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The right ventricle in tetralogy of Fallot: adaptation to sequential loading

Symakani

Genuchten²,

Zandbergen³

et al. 2023

Front. Pediatr.

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Right ventricular dysfunction is a major determinant of outcome in patients with complex congenital heart disease, as in tetralogy of Fallot. In these patients, right ventricular dysfunction emerges after initial pressure overload and hypoxemia, which is followed by chronic volume overload due to pulmonary regurgitation after corrective surgery. Myocardial adaptation and the transition to right ventricular failure remain poorly understood. Combining insights from clinical and experimental physiology and myocardial (tissue) data has identified a disease phenotype with important distinctions from other types of heart failure. This phenotype of the right ventricle in tetralogy of Fallot can be described as a syndrome of dysfunctional characteristics affecting both contraction and filling. These characteristics are the end result of several adaptation pathways of the cardiomyocytes, myocardial vasculature and extracellular matrix. As long as the long-term outcome of surgical correction of tetralogy of Fallot remains suboptimal, other treatment strategies need to be explored. Novel insights in failure of adaptation and the role of cardiomyocyte proliferation might provide targets for treatment of the (dysfunctional) right ventricle under stress.

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Section: Histopathology: What Do We Know?mentioning

confidence: 99%

Section: Histopathology: What Do We Know?mentioning

confidence: 99%

Section: Histopathology: What Do We Know?mentioning

confidence: 99%

Section: Current and Future Strategiesmentioning

confidence: 99%

See 2 more Smart Citations

The right ventricle in tetralogy of Fallot: adaptation to sequential loading

Symakani

Genuchten²,

Zandbergen³

et al. 2023

Front. Pediatr.

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“…RT-qPCR of specific genes (26)(27)(28)(29) representing cardiomyocyte stress [natriuretic peptide B (NPPB)], fetal gene switch [myosin heavy chain 7 (MYH7) to myosin heavy chain 6 (MYH6) ratio], profibrotic signaling [TIMP metallopeptidase inhibitor 1 (TIMP1)] and pathological hypertrophy [regulator of calcineurin (RCAN)1] were measured as described previously (30). Expression data were corrected for the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by means of the DDCT method.…”

Section: Gene Expression In Rv Tissuementioning

confidence: 99%

Female rats are less prone to clinical heart failure than male rats in a juvenile rat model of right ventricular pressure load

Bossers

Hagdorn

Koop

et al. 2022

American Journal of Physiology-Heart and Circulatory Physiology

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Sex is increasingly emerging as determinant of right ventricular (RV) adaptation to abnormal loading conditions. It is unknown, however, whether sex-related differences already occur in childhood. Therefore, this study aimed to assess sex differences in a juvenile model of early RV pressure load by pulmonary artery banding (PAB) during transition from pre- to post-puberty. 3-weeks old rat pups (n=57, 30-45g) were subjected to PAB or sham surgery. Animals were sacrificed either before or after puberty (4 and 8 weeks post-surgery, respectively). Male PAB rats demonstrated failure to thrive already after 4 weeks, whereas females did not. After 8 weeks, female PAB rats showed less clinical symptoms of RV failure than male PAB rats. RV pressure-volume analysis demonstrated increased end-systolic elastance after 4 weeks in females only, and a trend toward preserved end-diastolic elastance in female PAB rats compared to males (p=0.055). Histology showed significantly less RV myocardial fibrosis in female compared to male PAB rats 8 weeks after surgery. Myosin heavy chain 7/6 ratio switch and calcineurin signaling were less pronounced in female PAB rats, compared to males. In this juvenile rat model of RV pressure load, female rats appeared to be less prone to clinical heart failure, compared to males. This was driven by increased RV contractility before puberty, and better preservation of diastolic function with less RV myocardial fibrosis after puberty. These findings show that RV adaptation to increased loading differs between sexes already before the introduction of pubertal hormones.

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