Abstract
Objective: Cardiovascular disease (CVD) affects individuals across the lifespan with multiple cardiovascular (CV) risk factors increasingly present in young populations. The underlying mechanisms in early cardiovascular disease development are complex and still poorly understood. We therefore employed urinary proteomics as a novel approach to gain better insight into the early CVD-related molecular pathways based on a CVD-risk stratified approach. Design and Methods: This study included 964 apparently healthy (no self-reported chronic illnesses and free from clinical symptoms of CVD) black and white men and women (aged 20–30 years old) from the African-PREDICT study. Cardiovascular risk factors used for stratification included obesity, physical inactivity, tobacco use, high alcohol intake, hyperglycemia, dyslipidemia and hypertension. Participants were divided into low (0 risk factors), medium (1–2 risk factors) and high (3 or more risk factors) CV risk groups. We analyzed urinary peptidomics profiles by capillary electrophoresis time-of-flight mass spectrometry. Results: Upon adjusting for ethnicity, we identified 293 sequenced urinary peptides that were differentially expressed between the CV risk groups (all q-value smaller or equal to 0.01). These peptides included a lower abundance of collagen type I and a higher abundance of collagen type III derived peptides in the high compared to the low CV risk group. We also found a lower abundance of fibrinogen alpha and alpha antitrypsin 1 and a higher abundance of uromodulin derived peptides in the high compared to the low CV risk group (all q-value smaller or equal to 0.007). Conclusion: Our findings point out different abundances in collagen I and III between the high compared to low CV risk group, suggesting potential early alterations in the CV extracellular matrix.
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