P7 THE URINARY PEPTIDOMIC SIGNATURE OF AORTIC STIFFNESS REVEALS MOLECULAR PATHWAYS AND DRUG TARGETS

DOI

10.1016/j.artres.2017.10.060How to use a DOI?

Abstract

Background: Molecular pathways leading to stiffening of the central arteries are poorly understood. We searched for differentially expressed proteins by urinary peptidomic analysis in patients with arterial stiffness and healthy controls in a case–control study.

Methods: To identify urinary peptides associated with aortic stiffening, we applied capillary electrophoresis coupled to mass spectrometry. We compared 18 cardiovarscular disease-free patients with carotid-femoral pulse wave velocity (PWV > 10 m/s standardised to a heart rate of 75/minute as measured by the SphygmoCor method) with 18 controls matched for sex, age and mean arterial pressure.

Results: 69 urinary peptides had a different signal amplitude between cases and controls (P ≤ 0.049). Among 33 peptides with known sequence, 26 were members of the extracellular matrix family, including collagen type I α-1 and α-2, collagen type III α-1, collagen type IV α-5, collagens IX, XXI and XXVII. Collagen type I was down-regulated, whereas collagen type III was up-regulated. Epidermal growth factor receptor (EGFR), a key regulator of myoblast differentiation, and interactions of laminin with other proteins were down-regulated. Atherosclerosis signalling pathways and intrinsic prothrombin activation were the top pathways associated with increased PWV. Potential drug targets included collagen type IV α 3 and transforming growth factor β 3. Angiotensin-converting enzyme inhibitors, which are widely used for vascular protection, were among the possible therapeutic agents.

Conclusions: We suggest that stiffening of large elastic arteries involves changes of the extracellular matrix, as reflected by collagen turnover and regulation of myoblast differentiation. Pathway analysis identified potential drug targets, possibly amenable by angiotensin-converting enzyme inhibition.

Open Access

This is an open access article distributed under the CC BY-NC license.

TY  - JOUR
AU  - Zhen-Yu Zhang
AU  - Makis Izoidakis
AU  - Wen-Yi Yang
AU  - Lutgarde Thijs
AU  - Fang-Fei Wei
AU  - Qi-Fang Huang
AU  - Joost Schanstra
AU  - Jens-Uwe Voigt
AU  - Tatiana Kuznetsova
AU  - Peter Verhamme
AU  - Antonia Vlahou
AU  - Harald Mischak
AU  - Jan Staessen
PY  - 2017
DA  - 2017/12/06
TI  - P7 THE URINARY PEPTIDOMIC SIGNATURE OF AORTIC STIFFNESS REVEALS MOLECULAR PATHWAYS AND DRUG TARGETS
JO  - Artery Research
SP  - 63
EP  - 63
VL  - 20
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2017.10.060
DO  - 10.1016/j.artres.2017.10.060
ID  - Zhang2017
ER  -