A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study

Abstract

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 early CVD-related molecular pathways based on a CVD risk stratification approach.This study included 964 apparently healthy (no self-reported chronic illnesses, free from clinical symptoms of CVD) black and white men and women (aged 20-30 years old) from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (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 risk factors) CV risk groups. We analyzed urinary peptidomics by capillary electrophoresis time-of-flight mass spectrometry.After adjusting for ethnicity, sex and age, 65 sequenced urinary peptides were differentially expressed between the CV risk groups (all q-values≤0.01). These peptides included a lower abundance of collagen type I-and III-derived peptides in the high compared to the low CV risk group. With regard to noncollagen peptides, we found a lower abundance of alpha-1antitrypsin fragments in the high compared to the low CV risk group (all q-values≤0.01).Our findings indicate lower abundances of collagen types I and III in the high compared to the low CV risk group, suggesting potential early alterations in the CV extracellular matrix.

Urinary Peptidomics and Pulse Wave Velocity: The African-PREDICT Study

“…With regard to urinary peptidomics analyses, capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS) was performed using a P/ACE MDQ capillary electrophoresis system (Beckman Coulter, Fullerton, USA) coupled with a microTOF mass spectrometer (Bruker Daltonic, Bremen, Germany) as previously described . A detailed description on the biochemical analysis, sample preparation, and identification of urinary peptidomics was published previously …”

“…A detailed description of questionnaires, physical activity monitoring, and anthropometric, cardiovascular, and biochemical measurements were previously described. 21 …”

“… 25 A detailed description on the biochemical analysis, sample preparation, and identification of urinary peptidomics was published previously. 21 …”

“…A detailed description of questionnaires, physical activity monitoring, and anthropometric, cardiovascular, and biochemical measurements were previously described. 21 Briefly, a general health and demographic questionnaire was completed for each participant. The Kuppuswamy's Socioeconomic status scale was used to calculate each participant's socio-economic score for a South African environment.…”

“…In a recent study on urinary proteomics and early CVD risk, we compared the urinary peptide abundances between low, medium, and high CVD risk groups and found that collagen type I and III- derived peptides were lower in the high compared to the low CVD risk group, suggesting potential early alterations in the vascular extracellular matrix . Therefore, we aimed to determine whether a measure of large artery stiffness (PWV) is associated with a urinary proteomics profile in young adults, with a specific focus on vascular-specific extracellular matrix proteins such as collagen type I and III.…”