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

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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-1-antitrypsin 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.

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Acknowledgements

We are grateful to all individuals who voluntarily participated in this study. The dedication of the support and research staff as well as students at the Hypertension Research and Training Clinic at the North-West University is also duly acknowledged.

Funding

The research funded in this manuscript is part of an ongoing research project financially supported by the South African Medical Research Council (SAMRC) with funds from the National Treasury under its Economic Competitiveness and Support Package; the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (GUN 86895); the SAMRC with funds received from the South African National Department of Health, GlaxoSmithKline R&D (Africa Non-Communicable Disease Open Lab grant), the UK Medical Research Council and with funds from the UK Government’s Newton Fund; and corporate social investment grants from Pfizer (South Africa), Boehringer-Ingelheim (South Africa), Novartis (South Africa), the Medi Clinic Hospital Group (South Africa) and kind contributions from Roche Diagnostics (South Africa). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in this regard.

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Authors and Affiliations

  1. Hypertension in Africa Research Team (HART), North-West University (Potchefstroom Campus), Potchefstroom, South Africa

    Dalene de Beer, Catharina M. C. Mels, Aletta E. Schutte & Ruan Kruger

  2. MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, South Africa

    Catharina M. C. Mels, Aletta E. Schutte & Ruan Kruger

  3. School of Population Health, University of New South Wales; The George Institute for Global Health, Sydney, NSW, Australia

    Aletta E. Schutte

  4. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

    Christian Delles, Sheon Mary & William Mullen

  5. Mosaiques Diagnostics GmbH, Hannover, Germany

    Harald Mischak

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  1. Dalene de Beer
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Correspondence to Ruan Kruger.

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HM is the co-founder and co-owner of Mosaiques Diagnostics. All other authors have no conflicts of interest to declare.

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de Beer, D., Mels, C.M.C., Schutte, A.E. et al. A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study. Hypertens Res 46, 485–494 (2023). https://doi.org/10.1038/s41440-022-01097-7

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