Expression of vascular endothelial growth factor in patients with acute myocardial infarction
Yukihiro Hojo, MD, PhDa,
Uichi Ikeda, MD, PhDa,
Yun Zhu, MDa,
Motoi Okada, MDa,
Shuichi Ueno, MDa,
Hiroshi Arakawa, MDa,
Hideyuki Fujikawa, MD, PhDa,
Taka-aki Katsuki, MD, PhDa and
Kazuyuki Shimada, MD, PhDa
a Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi, Japan
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Figure 1 Changes in serum VEGF levels in patients with AMI. Serum was isolated from peripheral blood without using heparin. Patients receiving systemic administration of heparin were excluded. The data on day 1 represent serum VEGF levels at the time of admission. Serum VEGF levels in AMI patients were significantly higher than those in control subjects on day 14 after the onset (163 ± 26.2 vs. 68.7 ± 16.4 pg/ml). Solid circles: mean serum VEGF levels in AMI patients; open circles: mean serum VEGF levels in control subjects. Values are expressed as mean ± SEM. *p < 0.05 compared with control subjects.
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Figure 2 VEGF production by PBMCs isolated from AMI patients and control subjects. Anticoagulated peripheral blood was obtained from patients with AMI and normal subjects. PBMCs were isolated using a Mono-Poly resolving medium and cultured in an RPMI medium supplemented with 10% FBS at a concentration of 5 x 106 cells/ml in a humidified atmosphere of 5% CO2 at 37°C. The supernatants were collected 6, 12 and 24 h after incubation. VEGF levels in the culture medium increased time-dependently until 24 h after incubation. Solid circles: mean VEGF levels in the supernatant of cultured PBMCs in AMI patients seven days after onset; open circles: mean VEGF levels in the supernatant of cultured PBMCs in normal subjects. Values are expressed as mean ± SEM. *p < 0.05 compared with control subjects.
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Figure 3 VEGF levels in the supernatant of cultured PBMCs over the course of AMI. VEGF levels in the supernatant of cultured PBMCs after incubation for 24 h were defined as "PBMC-VEGF levels." PBMC-VEGF levels in the patients were significantly higher than those of control subjects (129 ± 23.1 pg/ml) from 7 to 14 days after the onset of AMI, with a peak on day 7 (344 ± 63.5 pg/ml). Solid circles: mean PBMC-VEGF levels in AMI patients; open circles: mean PBMC-VEGF levels in normal subjects. Values are expressed as mean ± SEM. *p < 0.05 compared with control subjects.
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Figure 4 Correlations between VEGF levels and CPK levels. A, A significant positive correlation was found between maximum serum VEGF levels and maximum CPK levels in the course of AMI (r = +0.64, p < 0.001). Patients receiving heparin for over seven days were excluded because maximum serum VEGF levels can be underestimated in such patients. B, No significant correlation was found between maximum PBMC-VEGF levels and maximum CPK levels.
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Figure 5 Changes in LVEF during the course of AMI. We performed left ventriculography (LVG) at the time of admission followed by re-LVG before discharge on 25 patients. LVEFs were analyzed by LVG. Mean LVEF levels did not change significantly in the course of AMI (from 54.1 ± 2.6% to 54.6 ± 1.8%).
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Figure 6 VEGF levels and left ventricular function. We divided 25 patients into two groups according to the changes in LVEF evaluated by LVG. Group A (n = 9): AMI patients who did not show decreases in LVEF during the course of AMI; group B (n = 16): AMI patients who showed decreases in LVEF during the course of AMI. A, There was no significant difference between maximum serum VEGF levels between group A and B patients (238 ± 79.8 vs. 135 ± 32.6 pg/ml). B, Group A patients showed significantly higher maximum PBMC-VEGF levels than group B patients (916 ± 119 vs. 374 ± 70.1 pg/ml, p < 0.05).
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