OBJECTIVES: Due to potential therapeutic value of vascular endothelial growth factor (VEGF) in coronary artery disease, the effect and mechanism of VEGF in human arteries used as coronary bypass grafts become important but not fully understood. VEGF-mediated endothelial regulation in vasorelaxation was studied in internal mammary artery (IMA) and radial artery (RA), compared with that of the classical agent-acetylcholine (ACh). The role of nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF) was investigated. METHODS: VEGF- and ACh-induced responses were measured in RA and IMA with or without endothelium and in the absence or presence of inhibitors of nitric oxide synthase or prostacyclin. In addition, the VEGF-induced PGI2 was measured by enzyme immunoassay. RESULTS: VEGF induced similar relaxation in RA (59.2+/-9.3%) and IMA (56.1+/-6.4%) that was significantly inhibited by N(omega)-nitro-L-arginine (L-NNA) plus oxyhemoglobin (HbO) (IMA: 24.9+/-4.3%, P=0.03 vs. RA: 25.0+/-8.6%, P=0.01) or by indomethacin (INDO) (IMA: 21.8+/-2.5%, P=0.000 vs. RA: 30.0+/-6.6%, P=0.04) with more inhibition in IMA than RA (P<0.05). In addition, the VEGF-induced PGI2 was significantly higher in IMA than RA (11.5+/-2.1 vs. 4.9+/-1.1 pg/ml/mg, P=0.002). INDO+L-NNA+HbO reduced the VEGF-induced relaxation to 20.8+/-4.6% in RA vs. 4.8+/-1.6% in IMA (P=0.01). In contrast, the maximal relaxation induced by ACh in RA (55.9+/-6.0%) and IMA (48.5+/-5.3%) was largely inhibited by L-NNA in IMA and RA (14.7+/-3.0%, P=0.000 vs. 15.2+/-3.2%, P=0.004) but little affected by INDO. CONCLUSIONS: VEGF induces similar relaxation in IMA and RA with significantly more PGI2-mediated relaxation and higher stimulated PGI2 level in IMA but more EDHF-mediated relaxation in RA. In comparison, ACh-induced relaxation mainly depends on NO. Thus, our study reveals a significant difference in the mechanism of the endothelium-dependent relaxation induced by VEGF and ACh.
OBJECTIVES: Due to potential therapeutic value of vascular endothelial growth factor (VEGF) in coronary artery disease, the effect and mechanism of VEGF in human arteries used as coronary bypass grafts become important but not fully understood. VEGF-mediated endothelial regulation in vasorelaxation was studied in internal mammary artery (IMA) and radial artery (RA), compared with that of the classical agent-acetylcholine (ACh). The role of nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF) was investigated. METHODS:VEGF- and ACh-induced responses were measured in RA and IMA with or without endothelium and in the absence or presence of inhibitors of nitric oxide synthase or prostacyclin. In addition, the VEGF-induced PGI2 was measured by enzyme immunoassay. RESULTS:VEGF induced similar relaxation in RA (59.2+/-9.3%) and IMA (56.1+/-6.4%) that was significantly inhibited by N(omega)-nitro-L-arginine (L-NNA) plus oxyhemoglobin (HbO) (IMA: 24.9+/-4.3%, P=0.03 vs. RA: 25.0+/-8.6%, P=0.01) or by indomethacin (INDO) (IMA: 21.8+/-2.5%, P=0.000 vs. RA: 30.0+/-6.6%, P=0.04) with more inhibition in IMA than RA (P<0.05). In addition, the VEGF-induced PGI2 was significantly higher in IMA than RA (11.5+/-2.1 vs. 4.9+/-1.1 pg/ml/mg, P=0.002). INDO+L-NNA+HbO reduced the VEGF-induced relaxation to 20.8+/-4.6% in RA vs. 4.8+/-1.6% in IMA (P=0.01). In contrast, the maximal relaxation induced by ACh in RA (55.9+/-6.0%) and IMA (48.5+/-5.3%) was largely inhibited by L-NNA in IMA and RA (14.7+/-3.0%, P=0.000 vs. 15.2+/-3.2%, P=0.004) but little affected by INDO. CONCLUSIONS:VEGF induces similar relaxation in IMA and RA with significantly more PGI2-mediated relaxation and higher stimulated PGI2 level in IMA but more EDHF-mediated relaxation in RA. In comparison, ACh-induced relaxation mainly depends on NO. Thus, our study reveals a significant difference in the mechanism of the endothelium-dependent relaxation induced by VEGF and ACh.
Authors: Stephen J H Dobbin; Mark C Petrie; Rachel C Myles; Rhian M Touyz; Ninian N Lang Journal: Clin Sci (Lond) Date: 2021-01-15 Impact factor: 6.124
Authors: Eduardo Ferrero; María Dolores Mauricio; Miriam Granado; Oscar García-Villar; Martín Aldasoro; José María Vila; Manuel Hidalgo; Jorge Luis Ferrero; Nuria Fernández; Luis Monge; Angel Luis García-Villalón Journal: Biomed Res Int Date: 2013-11-10 Impact factor: 3.411