Retinol-binding protein 4 levels and susceptibility to ischaemic events in men.
BACKGROUND
Many efforts in cardiovascular medicine have been focused in the identification of patients at risk of developing an acute ischaemic event. Biomarker discovery studies have become an essential research area, being proteomic technologies an excellent tool for biomarker identification. By applying proteomic approaches, we have detected changes in retinol-binding protein 4 (RBP4) in acute new-onset myocardial infarction patients (AMI) and in high-risk patients with heterozygous familial hypercholesterolaemia (FH).


METHODS
Differential serum proteome was analysed by two-dimensional electrophoresis and MALDI-TOF/TOF. Validation studies were performed by ELISA, and functional effects of RBP4 were tested in cell culture experiments.


RESULTS
Retinol-binding protein 4 proteomic characterization depicted two spots (pI = 5·4;Mw = 23·01/22·78 kDa) with decreased intensity in AMI patients. Total serum RBP4 levels were decreased in AMI patients (N = 68) compared with controls (N = 132; P < 0·0001). RBP4 was also decreased in FH patients who had an ischaemic event 2 years (±0·3) after their inclusion compared with FH patients without any cardiovascular episode at follow-up (P < 0·001; N = 187). In both cases, changes were limited to men. RBP4 induced a significant increase in eNOS expression in human endothelial vascular cells and in prostaglandin I2 release in coronary vascular smooth muscle cells.


CONCLUSIONS
We show decreased serum RBP4 levels in men in the acute phase of AMI, being this decrease already detected in men with FH previous to the presentation of an ischaemic event. The decrease in RBP4 levels could confer an increased susceptibility to the precipitation of an ischaemic event that could be mediated by the decrease in its vasculoprotective properties through NO and PGI2 .
Cardiovascular Research Center (CSIC-ICCC), Barcelona, Spain; Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
Judit
J
Cubedo
Teresa
T
Padró
Juan
J
Cinca
Pedro
P
Mata
Rodrigo
R
Alonso
Lina
L
Badimon
D000328:Adult; D015415:Biomarkers; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D004586:Electrophoresis; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D040901:Proteomics; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism* / Q000494:pharmacology; D012737:Sex Factors; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D009569:Nitric Oxide; D011464:Epoprostenol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
Acute myocardial infarction; RBP4; familial hypercholesterolaemia; ischaemic event; proteomics; vascular homeostasis