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Quantitative plasma proteomic analysis in children after superior cavopulmonary anastomosis with pulmonary arteriovenous malformations

Pediatric Research (2024)Cite this article

Abstract

Approximately 1000 children are born every year in the United States with one effective cardiac pumping chamber, or single ventricle heart disease. One of the early causes of mortality in this population is pulmonary arteriovenous malformations (PAVMs), which allow blood to bypass gas exchange in the lungs. PAVMs most frequently occur in children after superior cavopulmonary anastomosis (SCPA), a procedure that redirects venous blood from the upper body to the lungs. Because plasma proteins are in part responsible for directing angiogenesis, we hypothesized that differential protein concentrations would be observed in superior caval blood among children after SCPA according to PAVM status. We performed quantitative plasma proteomics from 11 children with PAVMs and in seven children without PAVMs; an additional 11 children with Fontan circulation were included as a reference. Among children with SCPA, there were no significant differences in the plasma proteomes for those with and without PAVMs. When comparing children with Fontan circulation to those with SCPA and PAVMs, 18 proteins exhibited differential expression (10 downregulated and eight upregulated) in superior caval plasma. These results suggest that factors other than, or in addition to, plasma proteins may be responsible for single ventricle patients’ susceptibility to PAVMs after SCPA.

Impact

  • What is the key message of your article? We did not identify significant differences in plasma proteins when comparing those children with and without pulmonary arteriovenous malformations (PAVMs) after superior cavopulmonary anastomosis (SCPA).

  • What does it add to the existing literature? The etiology of PAVMs in this population is likely due to factors other than, or in addition to, differences in plasma proteins. What is the impact? Further studies are needed to identify causes of PAVMs among children after SCPA.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The present study was funded by a grant from the Arkansas Biosciences Institute.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Section of Cardiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Elijah H. Bolin, Amy M. Dossey, Michael J. Angtuaco & Dala Zakaria

  2. Arkansas Children’s Research Institute, Little Rock, AR, USA

    Elijah H. Bolin, Peter M. Mourani, Stephanie D. Byrum, Samuel G. Mackintosh, Amy M. Dossey, Michael J. Angtuaco, Dala Zakaria, Lawrence E. Greiten, Graham M. Strub, Haihong Zhang & Gresham T. Richter

  3. Department of Pediatrics, Critical Care Section, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Peter M. Mourani

  4. Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Stephanie D. Byrum & Samuel G. Mackintosh

  5. Department of Surgery, Section of Pediatric Cardiovascular Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Lawrence E. Greiten

  6. Department of Otolaryngology, Section of Pediatric Otolaryngology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Graham M. Strub, Haihong Zhang & Gresham T. Richter

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  1. Elijah H. Bolin
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Contributions

Substantial contributions to conception and design, acquisition of data, and analyzes/interpretation of data were performed by EHB, PMM, SDB, SGM, AMD, MJA, DZ, LEG, GMS, HZ, GTR. The article was drafted by EHB, and was critically reviewed for important intellectual content by PMM and SDB. All authors gave their final approval of the version submitted for publication.

Corresponding author

Correspondence to Elijah H. Bolin.

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Competing interests

The authors declare no competing interests.

Consent statement

The present study was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences, and informed consent was obtained from all patients; additionally, assent was obtained when appropriate for patients who were able to provide it.

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Bolin, E.H., Mourani, P.M., Byrum, S.D. et al. Quantitative plasma proteomic analysis in children after superior cavopulmonary anastomosis with pulmonary arteriovenous malformations. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03450-7

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