Vitiello Damien, Chaar Diana, Neagoe Paul-Eduard, Ducharme Anique, Carrier Michel, Pelletier Guy B, Racine Normand, Liszkowski Mark, Sirois Martin G, White Michel
Research Center, Montreal Heart Institute, Montréal, Qc Canada ; Université de Montréal, 5000 Belanger Street, Montreal, QC Canada.
Research Center, Montreal Heart Institute, Montréal, Qc Canada.
Vasc Cell. 2015 Apr 22;7:4. doi: 10.1186/s13221-015-0029-8. eCollection 2015.
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.
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).
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.
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.
血管内皮生长因子（VEGF）可能在心脏移植（CTx）后的同种异体移植物重塑中发挥作用。我们测量了CTx受者循环中VEGF-A165的水平，并同时检测了促炎因子（白细胞介素-8；IL-8）、抗炎因子（IL-1受体拮抗剂；IL-1RA）及其从中性粒细胞中的释放情况。
18名年龄为49.6±3.1岁、移植后145±20个月的CTx受者与35名健康对照（HC）受试者进行年龄匹配。在进行血浆评估的同时，分离、纯化循环中的中性粒细胞，并用载体（PBS）、N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP，10⁻⁷ M）、细菌脂多糖（LPS，1 μg/mL）或肿瘤坏死因子α（TNF-α，10 ng/mL）进行刺激。
与HC相比，CTx受者血浆中VEGF-A165水平降低了80%（HC为225±42，CTx为44±10 pg/mL；p<0.001）。IL-8和IL-1RA水平无差异。在基础或刺激条件下，CTx患者的中性粒细胞在受到刺激后释放VEGF-A165、IL-8和IL-1RA的能力显著降低，降低幅度在30%至88%之间。
与健康志愿者相比，长期CTx受者循环中VEGF-A165水平以及中性粒细胞介导的VEGF-A165、IL-1RA和IL-8释放显著降低。这些发现的机制和生理影响值得进一步研究。
