Endogenous vascular repair system in cardiovascular disease: The role of endothelial progenitor cells

Abstract

Progression of endothelial dysfunction is strongly associated with thickening of the vascular wall due to proliferative changes in the intima and media, infiltration of lipids, accumulation of pro-inflammatory cytokines, chemokines and macrophages (mononuclears), extracellular matrix deposition of collagen and occurrence of fibrosis.3,4 Later, modifications of normal anatomical architectonic and micro aneurism can occur, loss of capillary greed with increasing inter-capillary dimensions, lowering perfusion efficacy and inducing tissue ischemia/ hypoxia. [...]micro neovascularization as a result of hypoxia, accumulation of activated mononuclears in intima and sub-intima, triggers plaque instability, haemorrhage and eventually atherothrombosis.5 Finally, rigid vascular wall with altered vasodilation including capillary rarefaction and increased aortic diameter are usually described as core components of vascular remodelling accompanying with nature evolution of the CV disease.6 Vascular remodelling is triggered by wide spectrum of stimuli, such as mechanical (high blood pressure, shear stress), metabolic (lipids, hyperglycaemia, hyperuricemia, hyper-and hypothyroidisms, hyperphosphatemia), inflammatory (reactive oxygen species, inflammatory cytokines and chemokines), ischemia / hypoxia that may also close associate with senescence and vascular aging.7-9 There is large body of evidence of triggers able to epigenetically modify precursors, a process by which cells stop proliferating and become dysfunctional.10 In this context, vascular reparation is "impaired" and associated with dysfunctional responses, such endothelial dysfunction. Taken together, combination of CD45(-), CD31(+), CD 133(+), CD34(+) and CD309(+) or vWf(+) probably allows getting reliable purification of progenitor endothelial subsets from mononuclear cells with presentation of endothelial markers.21-23 The molecular features of EPCs are reported in detail in Table 1. [...]different populations of EPCs may sufficiently distinguish each other not just depending on their origin, but according to stage of differentiation into mature endothelial cells or smooth muscle cells. The population of EPCs with immune phenotypes CD34(+)CD31(+), CD34(+)CD31(+)CD146(+), CD34(+)CD31(+), CD105(+), and CD34(+)CD31(+)CD309(+) demonstrated higher proliferative potency to CD34(-) EPCs co-expressing CD31, CD309, CD105 and CD146 antigenes. [...]CD34(+) EPCs had reproduced tubes and colony shaping in the single-cell colony-formation investigation as well as they responded to angiogenic growth factors.24 In contrast, CD34(-) cells had limited ability to reproduce colonies or even had not these properties in vitro. [...]the repair ability of vasculature is dramatically lowered due to failed ability of EPCs differentiate to mature endothelial cells and completely restore vascular integrity and function.