Examining Multiple Protein Families in Connection with Single Ventricle Heart Disease

Research study background  

Infants with single ventricle heart disease (SVHD) often suffer from complications due to insufficient pulmonary blood flow caused by pulmonary vascular inadequacy.

Study authors at the Children’s Hospital Colorado Heart Institute identified key protein families linked to pulmonary vascular development and maintenance, which were found to be dysregulated in affected patients. These protein families included: 

• Matrix metalloproteinases  
• Tissue inhibitor of metalloproteinase   
• Fibroblast growth factors

This is the first study to report the comprehensive mapping of circulating levels of these protein families and their relationship to outcomes in SVHD.

The study population included 70 infants with SVHD undergoing stage 2 palliation and 24 healthy infants undergoing non-cardiac surgery.

Data collection and analysis:

• Pre-operative venous samples from both groups
• Percent of time in the first 48 hours after surgery with oxygen saturation <70%
• 39 matrix metalloproteinases, tissue inhibitor of metalloproteinase, fibroblast growth factors circulating protein abundances
• Multivariate modeling of candidate predictors

Findings:

• 21 of 39 proteins differed between cases and controls, with levels higher among cases for most proteins, including:  
  • 7 matrix metalloproteinases  
  • 2 tissue inhibitors of metalloproteinase  
  • 12 fibroblast growth factors   
• 6 proteins linked to post-stage 2 hypoxemia and length of stay  
• 4 proteins remained associated with each outcome after multivariable analysis  
• Increased matrix metalloproteinases 7 and decreased matrix metalloproteinases 8 associated with greater hypoxemia burden and longer length of stay

Conclusions

Infants with SVHD experience broad alterations in circulating levels of multiple protein families, with angiogenesis regulation and extracellular matrix maintenance as possible pathophysiological drivers.

Matrix metalloproteinases 7 and matrix metalloproteinases 8 concentration are potential biomarkers of risk for perioperative stage 2 vascular complications.