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Coronary Artery Disease and Aortic Valve Stenosis: A Urine Proteomics Study
Luís Perpétuo1,2, António S Barros2, Jéssica Dalsuco2
1iBiMED-Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.
Insights
Researchers identified key urinary proteins, TIMP1, MMP2, and von Willebrand factor (vWF), as potential biomarkers for early detection of coronary artery disease (CAD) and aortic valve stenosis (AVS). These proteins show increased levels in patients and correlate with cardiovascular risk factors.
Area of Science:
- Cardiovascular Research
- Proteomics
- Biomarker Discovery
Background:
- Coronary artery disease (CAD) and aortic valve stenosis (AVS) are prevalent heart conditions often co-occurring and sharing risk factors and pathogenesis.
- Early detection of these atherosclerotic diseases is crucial for timely intervention, but routine biomarkers are lacking.
- Urine offers a noninvasive source for potential biomarker identification.
Purpose of the Study:
- To identify novel urinary protein biomarkers for the early detection of CAD and/or AVS.
- To explore the potential of urine proteomics for differentiating patients with these conditions from healthy individuals.
Main Methods:
- Shotgun proteomics analysis of urine samples from patients with CAD/AVS and healthy controls.
- Identification and validation of differentially expressed proteins using independent cohorts.
- Analysis of protein-protein interaction networks and correlation with cardiovascular risk factors.
Main Results:
- TIMP1, MMP2, and von Willebrand factor (vWF) were significantly elevated (≥2.5×) in the urine of CAD/AVS patients.
- These proteins occupied central positions in identified protein-protein interaction networks.
- Urinary TIMP1 and vWF levels strongly correlated with high-density lipoprotein (HDL) cholesterol, a cardiovascular risk factor.
Conclusions:
- Urinary TIMP1, MMP2, and vWF are promising candidates for noninvasive biomarkers of CAD and AVS.
- These biomarkers may aid in the early diagnosis and risk stratification of patients with these common heart diseases.
- Further validation is warranted to establish their clinical utility in routine diagnostics.
Abstract:
Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively).
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