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

Abstract

Increased arterial stiffness is related to early vascular aging and is an independent predictor for cardiovascular disease and mortality. Molecular mechanisms underlying increased arterial stiffness are largely unexplored, especially at the proteome level. We aimed to explore the relationship between pulse wave velocity and urinary proteomics. We included 919 apparently healthy (no chronic illnesses) Black and White men and women (equally distributed) between 20 and 30 years from the African-PREDICT study. Capillary electrophoresis time-of-flight mass spectrometry was used to analyze the urinary proteome. We measured the carotid-femoral pulse wave velocity to estimate arterial stiffness. In the total group, pulse wave velocity correlated positively with collagen-derived peptides including collagen types I, II, III, IV, V, and IX and inversely with collagen type XI (adjusted for mean arterial pressure). Regarding noncollagen-derived peptides, pulse wave velocity positively correlated with polymeric immunoglobulin receptor peptides (n = 2) (all q-value ≤0.05). In multivariable adjusted analyses, pulse wave velocity associated positively and independently with seven urinary peptides (collagen type I, n = 5) (all p-value ≤0.05). We found significant positive and independent associations between pulse wave velocity and the collagen type I-derived peptides, suggesting that dysregulation of collagen type I in the extracellular matrix scaffold could lead to early onset of increased arterial stiffness.

Keywords: arterial stiffness; collagen type I; early vascular aging; pathway analysis; vascular extracellular matrix.

Figure 1

Regression analysis between pulse wave velocity and urinary peptides in the total group (n = 919), adjusted for mean arterial pressure. The bars represent the regression coefficient ‘r’, all q-value <0.05.

Figure 2

Multivariable adjusted analysis between pulse wave velocity and the identified urinary peptides (n = 7), adjusted for sex, age, mean arterial pressure, heart rate, body mass index, γ-glutamyl transferase, glycated hemoglobin, C-reactive protein, cotinine, low-density lipoprotein, and physical activity, all p < 0.05.