TY - JOUR
T1 - Reshaping the preterm heart
T2 - Shifting cardiac renin-angiotensin system towards cardioprotection in rats exposed to neonatal high-oxygen stress
AU - Bertagnolli, Mariane
AU - Dartora, Daniela R.
AU - Lamata, Pablo
AU - Zacur, Ernesto
AU - Mai Vo, Thuy-An
AU - He, Ying
AU - Beauchamp, Léonie
AU - Lewandowski, Adam J
AU - Cloutier, Anik
AU - Sutherland, Megan R.
AU - Santos, Robson A. S.
AU - Nuyt, Anne Monique
N1 - Funding Information:
Heart and Stroke Foundation of Canada (Quebec) Grants-in-aid (A.M. Nuyt), Canadian Institutes of Health Research (CIHR) grants MOP220771 (A.M. Nuyt) and Canada Fund for Innovation (A.M. Nuyt). R.A.S. Santos was supported by a Conselho Nacional de Desenvolvimento Científico e Tecnológico-Institutos Nacionais de Ciência e Tecnologia. grant and FAPEMIG–Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ-03139-16), D.R. Dartora was supported by a scholarship from the Coordination for the Improvement of Higher Education Personnel (CAPES); Ministry of Education in Brazil (Process number: 99999.011682/2013-02). M. Bertagnolli was supported by the Bourse d’excellence pour étudiants étrangers du Fonds québécois de la recherche en santé (FRQ-S), a Jacques-de Champlain/Société Québécoise d’Hypertension Artérielle fellowship award and a SickKids Foundation grant (NI20-1037). A.J. Lewandowski was supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/18/3/33292). P. Lamata was funded in part by the Wellcome Trust (209450/Z/17/Z). For the purpose of Open Access, the author has applied a CC BY public copyright license to any author accepted article version arising from this submission.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - Background: Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O
2) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O
2-induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1-7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O
2exposure. Methods: Sprague-Dawley pups were exposed to room air or 80% O
2from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry. Results: At P10, high O
2-exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin-Angio-(1-7) significantly improved LV function in the O
2-exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin-Angio-(1-7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O
2-exposed rats at P10 and P28. Conclusions: Our findings demonstrate LV remodeling changes induced by O
2-stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm.
AB - Background: Approximately 10% of infants are born preterm. Preterm birth leads to short and long-term changes in cardiac shape and function. By using a rat model of neonatal high-oxygen (80%O
2) exposure, mimicking the premature hyperoxic transition to the extrauterine environment, we revealed a major role of the renin-angiotensin system peptide Angio II (angiotensin II) and its receptor AT1 (angiotensin receptor type 1) on neonatal O
2-induced cardiomyopathy. Here, we tested whether treatment with either orally active compounds of the peptides Angio-(1-7) or alamandine included in cyclodextrin could prevent postnatal cardiac remodeling and the programming of cardiomyopathy induced by neonatal high-O
2exposure. Methods: Sprague-Dawley pups were exposed to room air or 80% O
2from postnatal day 3 (P3) to P10. Neonatal rats were treated orally from P3 to P10 and assessed at P10 and P28. Left ventricular (LV) shapes were characterized by tridimensional computational atlases of ultrasound images in addition to histomorphometry. Results: At P10, high O
2-exposed rats presented a smaller, globular and hypertrophied LV shape versus controls. Treatment with cyclodextrin-Angio-(1-7) significantly improved LV function in the O
2-exposed neonatal rats and slightly changed LV shape. Cyclodextrin-alamandine and cyclodextrin-Angio-(1-7) treatments similarly reduced hypertrophy at P10 as well as LV remodeling and dysfunction at P28. Both treatments upregulated cardiac angiotensin-converting enzyme 2 in O
2-exposed rats at P10 and P28. Conclusions: Our findings demonstrate LV remodeling changes induced by O
2-stress and the potential benefits of treatments targeting the cardioprotective renin-angiotensin system axis, supporting the neonatal period as an important window for interventions aiming at preventing cardiomyopathy in people born preterm.
UR - http://www.scopus.com/inward/record.url?scp=85134386363&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.122.19115
DO - 10.1161/HYPERTENSIONAHA.122.19115
M3 - Article
SN - 0194-911X
VL - 79
SP - 1789
EP - 1803
JO - Hypertension
JF - Hypertension
IS - 8
ER -