Decreased circulating and neutrophil mediated VEGF-A165 release in stable long-term cardiac transplant recipients.
BACKGROUND
Vascular endothelial growth factor (VEGF) may play a role on the allograft remodelling following cardiac transplantation (CTx). We measured the circulating levels of VEGF-A165 concomitantly with the proinflammatory (Interleukin-8; IL-8), anti-inflammatory (IL-1 receptor antagonist; IL-1RA) and their release from neutrophils of CTx recipients.


METHODS
Eighteen CTx recipients aged 49.6 ± 3.1 years, being transplanted for 145 ± 20 months were age-matched to 35 healthy control (HC) subjects. Concomitantly to plasma assessment, circulating neutrophils were isolated, purified and stimulated by vehicle (PBS), N-formyl-Met-Leu-Phe (fMLP, 10(-7) M), bacterial lipopolysaccharide (LPS, 1 μg/mL), or tumour necrosis factor alpha (TNF-α, 10 ng/mL).


RESULTS
Compared with HC, CTx recipients exhibited a decrease (-80%) in plasmatic levels of VEGF-A165 (225 ± 42 (HC) vs 44 ± 10 pg/mL (CTx); (p < 0.001). There were no differences in the levels of IL-8 and IL-1RA. Under basal or stimulated conditions, neutrophils from CTx patients exhibited a marked decrease ranging from -30 to -88% on their capacity to release VEGF-A165, IL-8 and IL-1RA upon stimulation.


CONCLUSIONS
Long-term CTx recipients exhibit a marked reduction in the circulating levels of VEGF-A165, as well as neutrophil-mediated release of VEGF-A165, IL-1RA and IL-8 compared to healthy volunteers. The mechanisms and physiological impacts of these findings deserve additional investigations.
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Damien
D
Vitiello
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Diana
D
Chaar
Research Center, Montreal Heart Institute, Montréal, Qc Canada.
Paul-Eduard
PE
Neagoe
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Anique
A
Ducharme
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Michel
M
Carrier
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Guy B
GB
Pelletier
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Normand
N
Racine
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Mark
M
Liszkowski
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Martin G
MG
Sirois
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Michel
M
White
Allograft; Cardiac transplantation; Inflammation; Interleukin-1 recipient antagonist; Neutrophils; VEGF-A165