Endothelial progenitor cells: novel biomarker and promising cell therapy for cardiovascular disease

Abstract

Bone-marrow-derived EPCs (endothelial progenitor cells) play an integral role in the regulation and protection of the endothelium, as well as new vessel formation. Peripheral circulating EPC number and function are robust biomarkers of vascular risk for a multitude of diseases, particularly CVD (cardiovascular disease). Importantly, using EPCs as a biomarker is independent of both traditional and non-traditional risk factors (e.g. hypertension, hypercholesterolaemia and C-reactive protein), with infused ex vivo-expanded EPCs showing potential for improved endothelial function and either reducing the risk of events or enhancing recovery from ischaemia. However, as the number of existing cardiovascular risk factors is variable between patients, simple EPC counts do not adequately describe vascular disease risk in all clinical conditions and, as such, the risk of CVD remains. It is likely that this limitation is attributable to variation in the definition of EPCs, as well as a difference in the interaction between EPCs and other cells involved in vascular control such as pericytes, smooth muscle cells and macrophages. For EPCs to be used regularly in clinical practice, agreement on definitions of EPC subtypes is needed, and recognition that function of EPCs (rather than number) may be a better marker of vascular risk in certain CVD risk states. The present review focuses on the identification of measures to improve individual risk stratification and, further, to potentially individualize patient care to address specific EPC functional abnormalities. Herein, we describe that future therapeutic use of EPCs will probably rely on a combination of strategies, including optimization of the function of adjunct cell types to prime tissues for the effect of EPCs.

Transplantation of bone marrow-derived endothelial progenitor cells attenuates myocardial interstitial fibrosis and cardiac dysfunction in streptozotocin-induced diabetic rats

“…The characteristics of EPCs delineated in the present study are consistent with the common features of EPCs reported in previous studies. In addition, the co-expression of these markers also characterizes the isolated EPCs at a specific maturation stage (14). EPCs have been reported to ameliorate acute myocardial infarction and diabetic erectile dysfunction by promoting angiogenesis (29)(30).…”

“…Furthermore, an altered status of circulating EPCs represents a diagnostic biomarker for endothelial dysfunction and individual diseases. Due to their role in enhacing angiogenesis, there has been a growing interest in using EPCs as therapeutic agents to supply the potent origin of neovascularization under pathological conditions (13)(14)(15)(16). Endothelial dysfunction is a hallmark of diabetic vascular complications and reduction in circulating EPCs and functional impairment of cultured EPCs have been reported in type I and II diabetic patients (17,18).…”

Effects of the ginkgo biloba extract on the superoxide dismutase activity and apoptosis of endothelial progenitor cells from diabetic peripheral blood

“…In clinical circumstances, EPC number and function changes alone cannot then adequately affect the progression of blood vessel disease. These changes were also observed in the outer membranes of cells such as smooth muscle cells and macrophages (Sen et al, 2011). In the treatment of diabetic vascular disease with the EPCs, therefore, a joint strategy may be needed to adjust the function of surrounding cells to ultimately affect EPCs and achieve the most optimal treatment regimens.…”

Endothelial Progenitor Cells Dysfunction in Diabetes Mellitus

“…Most importantly, EPCs isolated from peripheral blood of the patients with known CAD have exhibited an impaired migratory and weak proliferative response [50], which have confirmed being of "EPC impaired phenotypes" pre-existing in subjects with CV risk factors prior established CV disease [55,56]. However, the circulating level of EPCs in patients with established higher CV risk is very variable and does not fully correlate with number of CV risk factors [57,58], although number of BM-EPCs has closely predicted asymptomatic atherosclerosis [59,60] and CV disease [61]. One found that lowered number of circulating EPCs originated from bone marrow have accompanied with hypercholesterolemia-induced expression of pro-inflammatory molecules by the vessel wall [62].…”