Endothelial progenitor cells in atherosclerosis

Abstract

Endothelial progenitor cells (EPCs) are involved in the maintenance of endothelial homoeostasis and in the process of new vessel formation. Experimental and clinical studies have shown that atherosclerosis is associated with reduced numbers and dysfunction of EPCs; and that medications alone are able to partially reverse the impairment of EPCs in patients with atherosclerosis. Therefore, novel EPC-based therapies may provide enhancement in restoring EPCs' population and improvement of vascular function. Here, for a better understanding of the molecular mechanisms underlying EPC impairment in atherosclerosis, we provide a comprehensive overview on EPC characteristics, phenotypes, and the signaling pathways underlying EPC impairment in atherosclerosis.

Figure 1

Schematic representation of endothelial progenitor cell (EPC) generation and the processes by which EPCs differentiate to mature endothelial cells (ECs). Multiple types of EPCs contribute to the accumulation of circulating EPCs, e.g.: bone marrow sub type (BM), vascular wall subtype (VW), and myeloid subtype. Bone marrow is the major reservoir of multiple types of circulating EPCs. Multiple factors stimulate or inhibit the processes of EPCs differentiating to ECs. (+): stimulate; (−): inhibit. (?): uncertain. VEGFR-2: vascular endothelial growth factor receptor-2; KDR: kinases insert domain receptor. vWF: von willebrand Factor. VE-cad: vascular endothelial cadherin. CD146−: cell surface marker. PPAR-gamma: Peroxisome proliferator-activated receptor gamma. CRP-inhibitors: C-reactive protein inhibitor. TNF blockers: tumor necrosis factor blocker. ACE-inhibitors: angiotensin converting enzyme inhibitors. G-CSF: granulocyte colony-stimulating factor. GM-CSF: granulocyte monocyte colony-stimulating factor. IL-1 beta: interlukin-1 beta. IL-8: interleukin-8. ICAM-1: intercellular adhesion molecule-1. SDF-1: stromal cell-derived factor-1. ADMA: asymmetric dimethylarginine. Ox-LDL: oxidized low-density lipoprotein.

Figure 2

Schematic summarizes the mechanisms through which the factors influence endothelial progenitor cell (EPC) homeostasis, survival and function. (+): stimulation. (−): inhibition. (↑): up-regulation. (↓): down-regulation. ROS: reactive oxygen species. CRP: C-reactive protein. OxLDL: oxidized low-density lipoprotein. LOX-1: lectin-like oxidized low density lipoprotein receptor. eNOS: endothelial nitric oxide synthase. VEGF: vascular endothelial growth factor. VEGFR2: vascular endothelial growth factor receptor 2. ATII: angiotensin II. SDF-1alpha: stromal cell-derived factor-1alpha. CXCR4: Chemokine receptor type 4. EPO: erythropoietin. G-CSF: granulocyte colony-stimulating factor. GM-CSF: granulocyte monocyte colony-stimulating factor. IL-6: interlukin-6. MMP-9: matrix metalloproteinase-9. TNF-alpha: tumor necrosis factor-alpha. LPS: Lipopolysaccharide. P38 MAPK: P38 mitogen-activated protein kinase. AGE: advanced glycation end products. PI3K/Akt: phosphatidylinositol-3/Akt pathway. FoxOs: forkhead family of transcription factor.