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Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft vasculopathy
Neha Singh1, Ward Heggermont2, Steffen Fieuws3
1Centre for Molecular and Vascular Biology.
Insights
Endothelium-enriched microRNAs (miRNAs) show promise in diagnosing cardiac allograft vasculopathy (CAV) after heart transplantation. These specific miRNAs, miR-126-5p and miR-92a-3p, improve diagnostic accuracy beyond traditional clinical factors.
Area of Science:
- Cardiology
- Molecular Biology
- Transplantation Medicine
Background:
- Cardiac allograft vasculopathy (CAV) significantly impacts long-term heart transplant recipient survival.
- Developing prediction models using circulating biomarkers could enhance clinical decision-making.
- The endothelium's role in CAV pathogenesis suggests endothelial microRNAs (miRNAs) as potential diagnostic markers.
Purpose of the Study:
- To evaluate if endothelium-enriched miRNAs can differentiate heart transplant recipients with and without CAV.
- To assess the diagnostic capability of specific miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, miR-126-5p) in CAV detection.
Main Methods:
- Cross-sectional study of 52 heart transplant recipients (5-15 years post-transplant) undergoing coronary angiography.
- Quantification of circulating endothelium-enriched miRNAs using real-time reverse transcription polymerase chain reaction.
- Logistic regression models and concordance (C) statistic were used to evaluate discriminative ability.
Main Results:
- Higher plasma levels of miR-210-5p, miR-92a-3p, miR-126-3p, and miR-126-5p were observed in patients with CAV.
- Recipient age, serum creatinine, miR-92a-3p, and miR-126-5p showed predictive value in univariable models.
- Multivariable models indicated that miR-126-5p and miR-92a-3p, along with age and creatinine, significantly improved CAV prediction (C statistic = 0.800).
Conclusions:
- Endothelium-enriched miRNAs, specifically miR-126-5p and miR-92a-3p, possess significant diagnostic ability for CAV.
- These miRNAs offer added diagnostic value beyond established clinical predictors like age and creatinine.
- MiRNA profiling represents a promising avenue for non-invasive CAV diagnosis and management.
Background:
Cardiac allograft vasculopathy (CAV) is a limiting factor for the long-term survival of heart transplant recipients. Clinical decisions and care may be improved by the development of prediction models based on circulating biomarkers. The endothelium may play a central pathogenetic role in the development of CAV. We evaluated the hypothesis that endothelium-enriched microRNAs (miRNAs) discriminate between patients with and without CAV.
Methods:
This cross-sectional study recruited 52 patients undergoing coronary angiography between 5 and 15 years after heart transplantation. Circulating levels of endothelium-enriched miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, and miR-126-5p) were quantified by real-time reverse transcription polymerase chain reaction. The discriminative ability of logistic regression models was evaluated using the concordance (C) statistic.
Results:
Median plasma levels of miR-210-5p, miR-92a-3p, miR-126-3p, and miR-126-5p were 1.82-fold (p = not significant), 1.87-fold (p < 0.05), 1.94-fold (p = 0.074), and 1.59-fold (p = 0.060) higher in patients with CAV than in patients without CAV. Recipient age (C statistic = 0.689; 95% confidence interval [CI], 0.537-0.842), and levels of serum creatinine (C statistic = 0.703; 95% CI, 0.552-0.854), miR-92a-3p (C statistic = 0.682; 95% CI, 0.533-0.831), and miR-126-5p (C statistic = 0.655; 95% CI, 0.502-0.807) predicted CAV status in univariable models. In multivariable logistic regression models with recipient age and creatinine as covariates, miR-126-5p (chi-square = 4.37(1), p = 0.037), miR-92a-3p (chi-square = 6.01(1), p = 0.014), and the combination of miR-126-5p and miR-92a-3p (chi-square = 8.16(2), p = 0.017) added significant information. The model with age, creatinine, miR-126-5p, and miR-92a-3p as covariables conferred good discrimination between patients without and with CAV (C statistic = 0.800; 95% CI, 0.674-0.926).
Conclusions:
Endothelium-enriched miRNAs have diagnostic ability for CAV beyond clinical predictors.
