Decreased circulating and neutrophil mediated VEGF-A165 release in stable long-term cardiac transplant recipients

Abstract

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-A ₁₆₅concomitantly 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-A ₁₆₅(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-A ₁₆₅, IL-8 and IL-1RA upon stimulation.

Conclusions

Long-term CTx recipients exhibit a marked reduction in the circulating levels of VEGF-A ₁₆₅, as well as neutrophil-mediated release of VEGF-A ₁₆₅, IL-1RA and IL-8 compared to healthy volunteers. The mechanisms and physiological impacts of these findings deserve additional investigations.