Post-weaning protein malnutrition induces myocardial dysfunction associated with oxidative stress and altered calcium handling proteins in adult rats

Abstract

Hypercaloric low-protein diet may lead to a state of malnutrition found in the low-income population of Northeastern Brazil. Although malnutrition during critical periods in the early life is associated with cardiovascular diseases in adulthood, the mechanisms of cardiac dysfunction are still unclear. Here we studied the effects of post-weaning malnutrition due to low protein intake induced by a regional basic diet on the cardiac contractility of young adult rats. In vivo arterial hemodynamic and in vitro myocardial contractility were evaluated in 3-month-old rats. Additionally, protein content of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), total phospholamban (PLB) and phosphorylated at serine 16 (p-Ser(16)-PLB), α2-subunit of the Na(+)/K(+)-ATPase (α2-NKA), and Na(+)/Ca(2+) exchanger (NXC) and in situ production of superoxide anion (O2(-)) were measured in the heart. Blood pressure and heart rate increased in the post-weaning malnourished (PWM) rats. Moreover, malnutrition decreased twitch force and inotropic responses of the isolated cardiac muscle. Protein expression of SERCA, PLB/SERCA, and p-Ser(16)-PLB/PLB ratios and α2-NKA were decreased without changing NCX. The contraction dependent on transsarcolemmal calcium influx was unchanged but responsiveness to Ca(2+) and tetanic peak contractions were impaired in the PWM group. Myocardial O2(-) production was significantly increased by PWM. Our data demonstrated that this hypercaloric low-protein diet in rats is associated with myocardial dysfunction, altered expression of major calcium handling proteins, and increased local oxidative stress. These findings reinforce the attention needed for pediatric care, since chronic malnutrition in early life is related to increased cardiovascular risk in adulthood.

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Funding

This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Finance code 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Grants 303077/2017-4; 304557/2018-8; 433632/2018-6); and Fundação de Amparo à Pesquisa do Espírito Santo (FAPES - Grant 80707483 Universal 03/2017; 80600115, 73370215). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Conceptualization: Aucélia Cristina Soares Belchior, Carlos Peres da Costa, Dalton Valentim Vassallo, and Alessandra Simão Padilha

Methodology: Aucélia Cristina Soares Belchior and David Domingues Freire-Júnior

Formal analysis and investigation: Aucélia Cristina Soares Belchior, David Domingues Freire-Júnior, Leonardo dos Santos, and Alessandra Simão Padilha

Writing—original draft preparation: Leonardo dos Santos and Alessandra Simão Padilha

Writing—review and editing: Dalton Valentim Vassallo, Leonardo dos Santos, and Alessandra Simão Padilha

Funding acquisition: Dalton Valentim Vassallo, Leonardo dos Santos, and Alessandra Simão Padilha

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Correspondence to Leonardo dos Santos.

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Key points:

Post-weaning malnutrition leads to cardiac dysfunction in young adult rats.

Reduced inotropic responsiveness was a result of changes in the Ca2+ handling.

Increased myocardial oxidative stress may also be involved in cardiac dysfunction.

Adequate nutrition in early life should reduce cardiovascular risk in adulthood.

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Belchior, A.C.S., Freire-Júnior, D.D., Da Costa, C.P. et al. Post-weaning protein malnutrition induces myocardial dysfunction associated with oxidative stress and altered calcium handling proteins in adult rats. J Physiol Biochem (2021). https://doi.org/10.1007/s13105-021-00792-2

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Keywords

  • Hypercaloric low-protein diet
  • Undernutrition
  • Cardiac contractility
  • Ca2+ handling
  • Reactive oxygen species
  • Papillary muscle mechanics