Evaluation of circulating endothelial progenitor cells and the severity of transient ischemic attack

Abstract

Objective: Endothelial progenitor cells (EPCs) are believed to have a positive effect on maintaining endothelial integrity and participate in angiogenesis after cerebral infarction. Numerous studies have demonstrated that EPCs promote ischemic tissue angiogenesis after stroke. However, there are few studies on the relationship between the level of EPCs and the severity of transient ischemic attacks (TIAs). The current study aimed to investigate the evaluation value of EPCs and serum stromal cell-derived factor-1α(SDF-1α) levels on the severity of TIA.

Methods: A total of 144 patients with TIA who had an onset of symptoms within 24 h were enrolled and divided into a high-risk TIA (HR-TIA) group (79 cases) and a nonhigh-risk TIA (NHR-TIA) group (65 cases). Clinical data of these patients were collected. Flow cytometry (FCM) was used to measure the number of CD34⁺KDR⁺ EPCs, and enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of serum SDF-1α and vascular endothelial growth factor (VEGF). Fifteen healthy donors were selected as the normal control (NC) group. Circulating EPCs were isolated by density gradient centrifugation from the first 15 patients in the high-risk TIA group, the nonhigh-risk TIA group, and the NC group. A colony assay and MTT assay were used to determine the proliferation ability of each group, and a Boyden chamber was used to determine the migration potential of EPCs.

Results: Compared with the nonhigh-risk group, patients in the high-risk TIA group were older and had a higher incidence of hypertension and diabetes and stroke recurrence. Patients in the high-risk TIA group had higher levels of triglycerides, cholesterol, and low-density lipoprotein. However, there were no significant differences between the two groups in sex, time from onset to blood draw, smoking, body mass index, or homocysteine (P > 0.05). The number of circulating EPCs in the nonhigh-risk TIA group was higher than that in the high-risk TIA group (P < 0.01). SDF-1α and VEGF levels in the nonhigh-risk TIA group were lower than those in the high-risk TIA group (P < 0.01). The results of multivariate regression analysis showed that age, hypertension, diabetes, smoking, and SDF-1α were risk factors for high-risk TIA, and EPCs were protective factors for high-risk TIA. EPCs were separated and cultured for 72 h. Compared with the NC group, EPCs functions were weakened in the high-risk TIA group and nonhigh-risk TIA group (P < 0.05). Compared with the nonhigh-risk TIA group, EPC functions were decreased in the high-risk TIA group (P < 0.01).

Conclusion: CD34⁺KDR⁺ EPCs are protective factors for high-risk TIA. The number of circulating CD34⁺KDR⁺ EPCs and the concentration of SDF-1α have important clinical value in predicting the progression of TIA to high-risk TIA.

Keywords: Endothelial progenitor cells; Stromal cell-derived factor-1α; Transient ischemic attack; Vascular endothelial growth factor.