Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes - Implications for cardiovascular in risk and effects of multifactorial intervention
Plasma vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in diabetes - Implications for cardiovascular in risk and effects of multifactorial intervention
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DOI：
10.2337/diacare.27.12.2918
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发表时间：
2004-12-01
期刊：
影响因子：
16.2
通讯作者：
Lip, GYH
中科院分区：
文献类型：
--
作者：
Lim, HS;Blann, AD;Lip, GYH
目的 - 血管内皮生长因子 (VEGF) 和血管生成素 (Ang)-1 和 Ang-2 是血管生成的介质。最近的数据表明，这些生长因子之间的平衡可能会影响血管内皮的完整性。由于糖尿病与内皮细胞扰动密切相关，因此我们研究了糖尿病患者中这些血管生成生长因子的血浆水平；它们与血糖、炎症和内皮损伤/功能障碍的关系；和。研究设计和方法 - 我们测量了 94 名糖尿病患者（38 名患有明显心血管疾病 [CVD）] 和 34 名正常对照受试者的血浆 VEGF、Ang-1 和 Ang-2，以及血浆血管性血友病因子 (vWf) 和尿白蛋白肌酐比（标记内皮损伤/功能障碍）和白细胞介素 (IL)-6。 结果 - 血浆伴或不伴 CVD 的糖尿病患者的 vWf (P = 0.009)、IL-6 (P < 0.001)、VEGF (P = 0.001) 和 Ang-2 (P = 0.001) 高于对照受试者，但 Ang-1 (P = 0.635) 较高。多变量分析显示，HbA(1c) 是血浆 VEGF (P = 0.032) 和 Ang-2 (P = 0.015) 的独立预测因子。在 94 名患者中，由 33 名患有 CVD 患者和 31 名无 CVD 患者组成的亚组参加了为期一年的强化心血管风险管理。治疗后，两组的 HbA(1c) 和 LDL 胆固醇均显着降低，同时血浆 vWf 和 VEGF 也相应降低（P < 0.001）。 Ang-2 仅在没有 CVD 的患者中下降（P < 0.001）。两组血浆 IL-6 水平均无显着变化。结论 - 血浆 Ang-2（但不是 Ang-1）与 VEGF 水平一样，在糖尿病患者中选择性升高，并且与内皮损伤/功能障碍指标相关，无论血管疾病如何。强化多因素干预与血浆 VEGF、vWf 和（无 CVD 患者）Ang-2 水平的降低相关，这可能反映了治疗后血管状况的改善。
OBJECTIVE - Vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-1 and Ang-2 are mediators of angiogenesis. More recent data suggest that the balance between these growth factors may affect vascular endothelial integrity. Because diabetes is closely associated With endothelial perturbation, we studied plasma levels of these angiogenic growth factors in patients with diabetes; their relationship with glycemia, inflammation, and endothelial damage/dysfunction; and the. effect of intensified cardiovascular risk management.RESEARCH DESIGN AND METHODS - We measured plasma VEGF, Ang-1, and Ang-2 alongside plasma von Willebrand factor (vWf) and urine albumin-to-creatinine ratio (marking endothelial damage/dysfunction) and interleukin (IL)-6 in 94 patients (38 with overt cardiovascular disease [CVD)] with diabetes and 34 normal control subjects.RESULTS - Plasma vWf (P = 0.009), IL-6 (P < 0.001), VEGF (P = 0.001), and Ang-2 (P = 0.001), but not Ang-1 (P = 0.635), were higher in diabetic patients with and without CVD than in control subjects. On multivariate analysis, HbA(1c) was an independent predictor of plasma VEGF (P = 0,032) and Ang-2 (P = 0.015). Of the 94 patients, a subgroup of 33 patients with and 31 patients without CVD participated in a year of intensified cardiovascular risk management. HbA(1c) and LDL cholesterol reduced significantly with treatment, along with associated reductions in plasma vWf and VEGF in. both groups (P < 0.001). Ang-2 decreased (P < 0.001) only in patients without CVD. There were no significant changes in plasma IL-6 levels in both groups.CONCLUSIONS - Plasma Ang-2 (but not Ang-1), like VEGF levels, are selectively elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction, regardless of vascular disease. Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment.