Difference in Serum Endostatin Levels in Diabetic Patients with Critical Limb Ischemia Treated by Autologous Cell Therapy or Percutaneous Transluminal Angioplasty

Abstract

The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008-2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO₂) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO₂ at 1 month after ACT ( r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.

Keywords: angiogenic factors; autologous cell therapy; critical limb ischemia; endostatin.

Figure 1.

Comparison of S-endostatin levels between patients after ACT and PTA. S-endostatin increased significantly at 1 and 3 months after ACT (***P < 0.001) in contrast to no significant changes of S-endostatin after PTA. ACT, autologous cell therapy; PTA, percutaneous transluminal angioplasty.

Figure 2.

Changes of TcPO₂ after revascularization. TcPO₂ increases significantly from baseline values both after ACT (***P < 0.001) and PTA (^††P < 0.01). ACT, autologous cell therapy; PTA, percutaneous transluminal angioplasty; TcPO₂, transcutaneous oxygen pressure.

Figure 3.

Comparison of kinetics of S-endostatin and TcPO₂ after ACT. Levels of TcPO₂ significantly increase from baseline values and remain elevated at 6 months after ACT (***P < 0.001), while S-endostatin levels increase at 1 and 3 months after ACT (^†††P < 0.001) to decrease to baseline values at 6 months. ACT, autologous cell therapy; TcPO₂, transcutaneous oxygen pressure.

Figure 4.

Correlation between S-endostatin and TcPO₂ at 1 month after ACT (r = 0.557; P < 0.001). ACT, autologous cell therapy; TcPO₂, transcutaneous oxygen pressure.