Endothelial Progenitor Cells: Potential Biomarkers for Diagnosis and Prognosis of Ischaemic Stroke

Ischaemic stroke develops through an interference with blood supply to the brain and continues to be one of the leading causes of morbidity and mortality in the World. Global medical statistics reveal that ~75% of all stroke patients are older than 65 years and that the stroke occurrence more than doubles every 10 years after the age of 55 in both men and women.

Although various mechanisms may alter the structure and function of the adult brain during the aging process, endothelial dysfunction is regarded as the main pathology that renders cerebral vessels susceptible to atherosclerosis and subsequent vascular events. Endothelial dysfunction also constitutes the main cause of vascular abnormality in most lacunar strokes which result from occlusion of one of the penetrating arteries deep within the brain. Cortical strokes represent another common form of ischaemic stroke and develop from an embolism from the heart or large arteries. As the endothelium maintains vascular balance through regulation of many distinct functions like vascular permeability, tone and inflammation, it is of crucial importance to preserve its integrity and function at all times to prevent age- and stroke-related vascular damage.

Recent studies show that bone marrow-derived endothelial progenitor cells (EPCs) play a key role in sustaining appropriate endothelial function by re-endothelialisation of blood vessels in adult brain and ischaemic settings. Like embryonic angioblasts, EPCs are equipped with an inherent capacity to circulate, proliferate and differentiate. Hence, the markers of endothelial maturity (KDR), immaturity (CD133) and stemness (CD34) must be simultaneously detected in relevant studies to identify all endothelial-committed and undifferentiated cells.

It is likely that environmental changes, like oxidative stress, inflammatory responses and nitric oxide availability, evoked by ischaemic injury and aging may also suppress the generation and function of EPCs. As mobilisation, recruitment and homing of EPCs to sites of vascular injury are mediated by various growth factors like the SDF-1 (stromal cell-derived factor-1), VEGF (vascular endothelial growth factor) and GCSF (granulocyte-colony stimulating factor), it is likely that the diminished expression of these factors may also negatively influence the number and function of EPCs.

Interestingly, while there is little data on functional and numerical alteration of EPCs during the chronic phase of stroke, current data regarding EPC levels during acute and subacute phases of disease are inconsistent in that stable, increased or decreased numbers have been reported as compared to healthy subjects.The time course of EPC release after acute cerebral infarction also remains inconclusive.